bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from BET inhibition sensitizes immunologically-cold Rb-deficient prostate cancer to immune checkpoint blockade
Authors: Olson Brian M. , Chaudagar Kiranj , Bao Riyue , Saha Sweta Sharma. , Hong Christina , Li Marguerite , Rameshbabu Srikrishnan , Chen Raymond , Thomas Alison , Patnaik Akash
Published: September 2024

Abstract
Non-T cell-inflamed immunologically “cold” tumor microenvironments (TME) are associated with poor responsiveness to immune checkpoint blockade (ICB), and can be sculpted by tumor cell genomics. Here we evaluated how Retinoblastoma (Rb) tumor suppressor loss of function (LOF), one of the most frequent alterations in human cancer and associated with lineage plasticity, poor prognosis and therapeutic outcomes, alters the TME, and whether therapeutic strategies targeting the molecular consequences of Rb loss enhance ICB efficacy. We performed bioinformatics analysis to elucidate the impact of endogenous Rb LOF on the immune TME in human primary and metastatic tumors. Next, we utilized isogenic murine models of Rb-deficient prostate cancer (PC) for in vitro and in vivo mechanistic studies to examine how Rb loss and bromodomain and extraterminal (BET) domain inhibition (BETi) reprograms the immune landscape, and evaluated in vivo therapeutic efficacy of BETi, singly and in combination with ICB and androgen deprivation therapy. Rb loss was enriched in non-T cell-inflamed tumors, and Rb-deficient murine tumors demonstrated decreased immune infiltration in vivo. The BETi JQ1 increased immune infiltration into the TME through enhanced tumor cell STING/NF-κB activation and type I interferon (IFN) signaling within tumor cells, resulting in differential macrophage and T cell-mediated tumor growth inhibition and sensitization of Rb-deficient PC to ICB. BETi can reprogram the immunologically cold Rb-deficient TME via STING/NF-κB/IFN signaling to sensitize Rb-deficient PC to ICB. These data provide the mechanistic rationale to test combinations of BETi and ICB in clinical trials of Rb-deficient PC.
Data from Arginase 1/2 inhibitor OATD-02: from discovery to first-in-man setup in cancer immunotherapy
Authors: Borek Bartlomiej , Nowicka Julita , Gzik Anna , Dziegielewski Marek , Jedrzejczak Karol , Brzezinska Joanna , Grzybowski Marcin , Stanczak Paulina , Pomper Paulina , Zagozdzon Agnieszka , Rejczak Tomasz , Matyszewski Krzysztof , Golebiowski Adam , Olczak Jacek , Lisiecki Kamil , Tyszkiewicz Magdalena , Kania Magdalena , Piasecka Sylwia , Cabaj Anna , Dera Paulina , Mulewski Krzysztof , Chrzanowski Jacek , Kusmirek Damian , Sobolewska Elzbieta , Magdycz Marta , Mucha Lukasz , Masnyk Marek , Golab Jakub , Nowotny Marcin , Nowak Elzbieta , Napiorkowska-Gromadzka Agnieszka , Pikul Stanislaw , Jazwiec Radoslaw , Dzwonek Karolina , Dobrzanski Pawel , Meyring Michael , Skowronek Krzysztof , Iwanowski Piotr , Zaslona Zbigniew , Blaszczyk Roman
Published: September 2024

Abstract
Pharmacological inhibition of the controlling immunity pathway enzymes arginases 1 and 2 (ARG1 and ARG2) is a promising strategy for cancer immunotherapy. Here, we report the discovery and development of OATD-02, an orally bioavailable, potent arginases inhibitor. The unique pharmacological properties of OATD-02 are evidenced by targeting intracellular ARG1 and ARG2, as well as long drug-target residence time, moderate to high volume of distribution, and low clearance which may jointly provide a weapon against arginase-related tumor immunosuppression and ARG2-dependent tumor cell growth. OATD-02 monotherapy had an antitumor effect in multiple tumor models and enhanced an efficacy of the other immunomodulators. Completed non-clinical studies and human pharmacokinetic predictions indicate a feasible therapeutic window and allow for proposing a dose range for the first-in-human clinical study in cancer patients.
Data from Efficacy and Imaging Enabled Pharmacodynamic Profiling of KRAS G12C Inhibitors in Xenograft and Genetically Engineered Mouse Models of Cancer
Authors: Lee Catherine , Jiang Ziyue Karen , Planken Simon , Manzuk Lisa K. , Ortiz Roberto , Hall Michael , Noorbehesht Kavon , Ram Sripad , Affolter Timothy , Troche Gabriel E. , Ihle Nathan T. , Johnson Theodore , Ahn Youngwook , Kraus Manfred , Giddabasappa Anand
Published: September 2024

Abstract
KRAS is one of the most commonly mutated oncogenes in lung, colorectal, and pancreatic cancers. Recent clinical trials directly targeting KRAS G12C presented encouraging results for a large population of non-small cell lung cancer (NSCLC), but resistance to treatment is a concern. Continued exploration of new inhibitors and preclinical models is needed to address resistance mechanisms and improve duration of patient responses. To further enable the development of KRAS G12C inhibitors, we present a preclinical framework involving translational, non-invasive imaging modalities (CT and PET) and histopathology in a conventional xenograft model and a novel KRAS G12C knock-in mouse model of NSCLC. We utilized an in-house developed KRAS G12C inhibitor (Compound A) as a tool to demonstrate the value of this framework in studying in vivo pharmacokinetic/pharmacodynamic (PK/PD) relationship and anti-tumor efficacy. We characterized the Kras G12C-driven genetically engineered mouse model (GEMM) and identify tumor growth and signaling differences compared to its Kras G12D-driven counterpart. We also find that Compound A has comparable efficacy to sotorasib in the Kras G12C-driven lung tumors arising in the GEMM, but like observations in the clinic, some tumors inevitably progress on treatment. These findings establish a foundation for evaluating future KRAS G12C inhibitors that is not limited to xenograft studies and can be applied in a translationally relevant mouse model that mirrors human disease progression and resistance.
Data from Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer
Authors: Ghosh Susmita , Fan Fan , Powell Reid T. , Roszik Jason , Park Yongsung , Stephan Clifford , Sebastian Manu , Tan Lin , Sorokin Alexey V. , Lorenzi Philip L. , Kopetz Scott , Ellis Lee M. , Bhattacharya Rajat
Published: September 2024

Abstract
Mutations in KRAS are found in more than 50% of tumors from patients with metastatic colorectal cancer (mCRC). However, direct targeting of most KRAS mutations is difficult; even the recently developed KRASG12C inhibitors failed to show significant benefit in patients with mCRC. Single agents targeting MEK, a downstream mediator of RAS, have also been ineffective in CRC. To identify drugs that can enhance the efficacy of MEK inhibitors we performed unbiased high-throughput screening using CRC spheroids. We used trametinib as the anchor drug and examined combinations of trametinib with the National Cancer Institute Approved Oncology Library version 5. The initial screen, and following focused validation screens, identified vincristine as being strongly synergistic with trametinib. In vitro, the combination strongly inhibited cell growth, reduced clonogenic survival, and enhanced apoptosis compared to monotherapies in multiple KRAS-mutant CRC cell lines. Furthermore, this combination significantly inhibited tumor growth, reduced cell proliferation, and increased apoptosis in multiple KRAS-mutant patient-derived xenograft mouse models. In vivo studies using drug doses that reflect clinically achievable doses demonstrated that the combination was well tolerated by mice. We further determined that the mechanism underlying the synergistic effect of the combination was due to enhanced intracellular accumulation of vincristine associated with MEK inhibition. The combination also significantly decreased p-mTOR levels in vitro, indicating that it inhibits both RAS-RAF-MEK and PI3K-AKT-mTOR survival pathways. Our data thus provide strong evidence that the combination of trametinib and vincristine represents a novel therapeutic option to be studied in clinical trials for patients with KRAS-mutant mCRC.
Data from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E-based Antibody-Drug Conjugate for treatment of Nectin-4-expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: September 2024

Abstract
Overexpression of nectin cell adhesion protein 4 correlates with cancer progression and poor prognosis in many human malignancies. Enfortumab vedotin (EV) is the first nectin-4-targeting antibody drug conjugate approved by the US Food and Drug Administration for treatment of urothelial cancer. However, inadequate efficacy has limited progress in the treatment of other solid tumors with EV. Furthermore, ocular, pulmonary, and hematological toxic side effects are common in nectin-4-targeted therapy, which frequently results in dose reduction and/or treatment termination. Thus, we designed a second generation nectin-4-specific drug, 9MW2821, based on interchain-disulfide drug conjugate technology. This novel drug contained a site-specifically conjugated humanized antibody and the cytotoxic moiety monomethyl auristatin E. The homogenous drug-antibody ratio and novel linker chemistry of 9MW2821 increased the stability of conjugate in the systemic circulation, enabling highly efficient drug delivery and avoiding off-target toxicity. In preclinical evaluation, 9MW2821 exhibited nectin-4 specific cell binding, efficient internalization, bystander killing, and equivalent or superior antitumor activity compared with EV in both cell-line-derived xenograft and patient-derived xenograft models. In addition, 9MW2821 demonstrated a favorable safety profile; the highest non-severely toxic dose in monkey toxicological studies was 6 mg/kg, with milder adverse events compare to EV. Overall, 9MW2821 is a nectin-4-directed, investigational antibody-drug conjugate based on innovative technology that endowed the drug with compelling preclinical antitumor activity and a favorable therapeutic index. The 9MW2821 antibody-drug conjugate is being investigated in a Phase I/II clinical trial (NCT05216965) in patients with advanced solid tumors.
Data from APR-246 enhances colorectal cancer sensitivity to radiotherapy
Authors: Xie Xuqin , Fan Chuanwen , Luo Bin , Zhang Jing , Jensen Lasse D. , Burman Jonas , Jonsson Carolin , Ljusberg Anna , Larsson Peter , Zhao Zengren , Sun Xiao-Feng
Published: September 2024

Abstract
p53 mutation is common and highly related to radiotherapy resistance in rectal cancer. APR-246, as a small molecule, can restore the tumor-suppressor function to mutant p53. There is no study on combining APR-246 with radiation in rectal cancer; therefore, we examined whether APR-246 sensitized colorectal cancer cells with different p53 status to radiation. The combination treatment had synergistic effects on HCT116p53-R248W/-(p53Mut) cells, followed by HCT116p53+/+(p53WT) cells, and exhibited an additive effect on HCT116p53-/-(p53Null) cells through inhibiting proliferation, enhancing reactive oxygen species, and apoptosis. The results were confirmed in zebrafish xenografts. Mechanistically, p53Mut and p53WT cells shared more activated pathways and differentially expressed genes following the combination treatment, compared to p53Null cells, although the combination treatment regulated individual pathways in the different cell lines. APR-246 mediated radio-sensitization effects through p53-dependent and -independent ways. The results may provide evidence for a clinical trial of the combination in rectal cancer patients.
Data from A targeted thorium-227 conjugate demonstrates efficacy in preclinical models of acquired drug resistance and combination potential with chemotherapeutics and antiangiogenic therapies
Authors: Zitzmann-Kolbe Sabine , Kristian Alexander , Zopf Dieter , Kamfenkel Claudia , Politz Oliver , Ellingsen Christine , Hilbig Jochen , Juul Mark U. , Fonslet Jesper , Nielsen Carsten H. , Schatz Christoph A. , Bjerke Roger M. , Cuthbertson Alan S. , Mumberg Dominik , Hagemann Urs B.
Published: September 2024

Abstract
Targeted alpha therapies (TATs) are an innovative class of for cancer treatment. The unique mode-of-action of TATs is the induction of deleterious DNA double-strand breaks. Difficult-to-treat cancers, such as gynecological cancers upregulating the chemoresistance P-glycoprotein (p-gp) and overexpressing the membrane protein mesothelin (MSLN), are promising targets for TATs. Here, based on the previous encouraging findings with monotherapy, we investigated the efficacy of the mesothelin-targeted thorium-227 conjugate (MSLN-TTC) both as monotherapy and in combination with chemotherapies and antiangiogenic compounds in ovarian (OvCa) and cervical cancer models expressing p-gp.
MSLN-TTC monotherapy showed equal cytotoxicity in vitro in p-gp-positive and negative cancer cells, while chemotherapeutics dramatically lost activity on p-gp-positive cancer cells. In vivo, MSLN-TTC exhibited dose-dependent tumor growth inhibition with T/C ratios of 0.03–0.44 in various xenograft models irrespective of p-gp expression status. Furthermore, MSLN-TTC was more efficacious in p-gp-expressing tumors than chemotherapeutics. In the MSLN-expressing ST206B OvCa PDX model, MSLN-TTC accumulated specifically in the tumor, which combined with pegylated liposomal doxorubicin (doxil), docetaxel, bevacizumab, or regorafenib treatment induced additive-to-synergistic antitumor efficacy and substantially increased response rates compared with respective monotherapies. The combination treatments were well tolerated and only transient decreases in white and red blood cells were observed.
In summary, we demonstrate that MSLN-TTC treatment shows efficacy in p-gp-expressing models of chemoresistance and has combination potential with chemo- and antiangiogenic therapies.
Data from T cell-intrinsic immunomodulatory effects of TAK-981 (subasumstat), a SUMO-activating enzyme inhibitor, in chronic lymphocytic leukemia
Authors: Lam Vi , Roleder Carly , Liu Tingting , Bruss Nur , Best Scott , Wang Xiaoguang , Phillips Tycel , Shouse Geoffrey , Berger Allison J. , Alinari Lapo , Wang Lili , Siddiqi Tanya , Pennock Nathan D. , Danilov Alexey V.
Published: September 2024

Abstract
Novel targeted agents used in therapy of lymphoid malignancies are recognized to have complex immune-mediated effects. Sumoylation, a posttranslational modification of target proteins by small ubiquitin-like modifiers (SUMO), regulates a variety of cellular processes indispensable in immune cell activation. Despite this, the role of sumoylation in T cell biology in context of cancer is not known. TAK-981 (subasumstat) is a small molecule inhibitor of the SUMO-activating enzyme (SAE) that forms a covalent adduct with an activated SUMO protein. Using T cells derived from patients with chronic lymphocytic leukemia (CLL), we demonstrate that targeting SAE activates type I interferon response. This is accompanied by largely intact T-cell activation in response to T-cell receptor engagement, with increased expression of CD69 and CD38. Furthermore, TAK-981 decreases Treg differentiation and enhances secretion of interferon-γ by CD4+ and CD8+ T-cells. These findings were recapitulated in mouse models, suggesting an evolutionarily conserved mechanism of T cell activation regulated by SUMO modification. Relevant to the consideration of TAK-981 as an effective agent for immunotherapy in hematological malignancies, we demonstrate that the downstream impact of TAK-981 administration is enhancement of the cytotoxic function of CD8+ T cells, thus uncovering immune implications of targeting sumoylation in lymphoid neoplasia.
Data from Safety and Tolerability of a Novel Anti-HER2 Antibody-Drug Conjugate (PF-06804103) in Patients With HER2-Expressing Solid Tumors: A Phase 1 Dose Escalation Study
Authors: Meric-Bernstam Funda , Calvo Emiliano , Lee Keun Seok , Moreno Victor , Park Yeon Hee , Rha Sun Young , Chalasani Pavani , Zhong Wei , Zhou Li , Pirie-Shepherd Steven , Leung Abraham CF. , Curigliano Giuseppe
Published: September 2024

Abstract
PF-06804103 is an anti-HER2 antibody-drug conjugate with auristatin payload. We evaluated its safety, tolerability, and antitumor activity in patients with advanced/unresectable or metastatic breast cancer and gastric cancer. This multicenter, open-label, first-in-human, phase 1 study (NCT03284723) comprised dose escalation (P1) and dose expansion (P2). In P1, adults with HER2+ breast or gastric cancer received PF-06804103 0.15–5.0 mg/kg intravenously once/21 days (Q3W); in P2, patients with HER2+ or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH]−) breast cancer received 3.0 or 4.0 mg/kg Q3W. The primary endpoints were dose-limiting toxicities (DLTs) and safety (P1), and objective response rate (ORR) assessed using RECIST v1.1 (P2). Ninety-three patients enrolled in P1 (n=47: HER2+ gastric cancer=22, HER2+ breast cancer=25) and P2 (n=46: HER2+ breast cancer=19, hormone receptor [HR]+ HER2-low breast cancer=27) received PF-06804103. Four patients (3.0- and 4.0-mg/kg groups, n=2 each) had DLTs (mostly Grade 3). Safety and efficacy results showed a dose–response relationship. Adverse events leading to treatment discontinuation (44/93, 47.3%) included neuropathy (11/93, 11.8%), skin toxicity (9/93, 9.7%), myalgia (5/93, 5.4%), keratitis (3/93, 3.2%), and arthralgia (2/93, 2.2%). Two (2/79, 2.5%) patients (P1, 4.0- and 5.0-mg/kg groups, n=1 each) achieved complete response; 21 (21/79, 26.6%) achieved partial response. In P2, ORR was higher in HER2+ compared with HR+ HER2-low breast cancer (3.0 mg/kg: 16.7% [2/12] vs 10.0% [1/10]; 4.0 mg/kg: 47.4% [9/19] vs 27.3% [3/11]). PF-06804103 demonstrated antitumor activity; however, adverse events led to discontinuation in 47.3% of patients. Safety and efficacy were dose-dependent.
Clinical trial registration: clinicaltrials.gov NCT03284723
Data from A Carbonic Anhydrase IX/SLC1A5 axis regulates glutamine metabolism dependent ferroptosis in hypoxic tumor cells
Authors: Venkateswaran Geetha , McDonald Paul C. , Chafe Shawn C. , Brown Wells S. , Gerbec Zachary J. , Awrey Shannon J. , Parker Seth J. , Dedhar Shoukat
Published: September 2024

Abstract
The ability of tumor cells to alter their metabolism to support survival and growth presents a challenge to effectively treat cancers. Carbonic anhydrase IX (CAIX) is a hypoxia-induced, metabolic enzyme that plays a crucial role in pH regulation in tumor cells. Recently, through a synthetic lethal screen, we identified CAIX to play an important role in redox homeostasis. In this study, we show that CAIX interacts with the glutamine transporter, solute carrier family 1 member 5 (SLC1A5), and coordinately functions to maintain redox homeostasis through the glutathione/glutathione peroxidase 4 (GSH/GPX4) axis. Inhibition of CAIX increases glutamine uptake by SLC1A5 and concomitantly increases GSH levels. The combined inhibition of CAIX activity and glutamine metabolism or the GSH/GPX4 axis results in an increase in lipid peroxidation and induces ferroptosis, both in vitro and in vivo. Thus, this study demonstrates co-targeting of CAIX and glutamine metabolism as a potential strategy to induce ferroptosis in tumor cells.
Data from MTX-13, a novel PTK7-directed antibody-drug conjugate with widened therapeutic index shows sustained tumor regressions for a broader spectrum of PTK7-positive tumors
Authors: Kong Chao , Pu Junyi , Zhao Qianqian , Weng Weining , Ma Linjie , Qian Yu , Hu Wenhao , Meng Xun , Meng Tao
Published: September 2024

Abstract
Protein tyrosine kinase 7 (PTK7) is a Wnt signaling pathway protein implicated in cancer development and metastasis. When using a potent microtubule inhibitor (Aur0101), PTK7-targeting antibody-drug conjugate (ADC), h6M24-vc0101 (PF-06647020/Cofetuzumab pelidotin) is efficacious only in limited tumor types with low response rates in a phase I trial. To improve patient response and to expand responding tumor types, we designed MTX-13, a PTK7-targeting ADC consisting of a novel antibody (Ab13) conjugated to eight molecules of Topoisomerase I inhibitor exatecan through T1000, a novel self-immolative moiety. MTX-13 exhibited PTK7-specific cell binding, efficient internalization and exatecan release to cause cytotoxic activity through DNA damage and apoptosis induction, and a strong bystander killing. MTX-13 displayed potent antitumor activities on CDX and PDX models from a wide range of solid tumors, significantly outperforming h6M24-vc0101. PTK7 was shown to be an actionable target in small cell lung cancer for which MTX-13 showed complete and durable responses. With a consistent overexpression of PTK7 in squamous cell carcinomas derived from diverse anatomic sites, strong potency of MTX-13 in this group of heterogenous tumors suggested a common treatment strategy. Finally, MTX-13 inhibited tumor growth and metastasis in an orthotopic colon cancer xenograft model. MTX-13 displayed a favorable pharmacokinetic and safety profile in monkey with a highest non-severely toxic dose (HNSTD) of >30 mg/kg, significantly higher than 3-5 mg/kg of HNSTD for h6M24-vc0101. The higher therapeutic index of MTX-13 bodes well for its clinical translation with a potential to expand responding patient population beyond that of current PTK7-targeting ADCs.
Data from Co-targeting Phosphoinositide 3-Kinase and Focal Adhesion Kinase Pathways Inhibits Proliferation of NF2 Schwannoma Cells
Authors: Hardin Haley M. , Dinh Christine T. , Huegel Julianne , Petrilli Alejandra M. , Bracho Olena , Allaf Abdulrahman , Karajannis Matthias A. , Griswold Anthony J. , Ivan Michael E. , Morcos Jacques , Gultekin Sakir H. , Telischi Fred F. , Liu Xue Zhong , Fernandez-Valle Cristina
Published: September 2024

Abstract
Neurofibromatosis Type 2 (NF2) is a tumor predisposition syndrome caused by germline inactivating mutations in the NF2 gene encoding the merlin tumor suppressor. Patients develop multiple benign tumor types in the nervous system including bilateral vestibular schwannomas. Standard treatments include surgery and radiation therapy, which may lead to loss of hearing, impaired facial nerve function and other complications. Kinase inhibitor monotherapies have been evaluated clinically for NF2 patients with limited success, and more effective non-surgical therapies are urgently needed. Schwannoma model cells treated with PI3K inhibitors upregulate activity of the focal adhesion kinase family as a compensatory survival pathway. We screened combinations of 13 clinically relevant PI3K and FAK inhibitors using human isogenic normal and merlin-deficient Schwann cell lines. The most efficacious combination was PI3K/mTOR inhibitor omipalisib with SRC/FAK inhibitor dasatinib. Sub-GI50 doses of the single drugs blocked phosphorylation of their major target proteins. The combination was superior to either single agent in promoting a G1 cell cycle arrest and produced a 44% decrease in tumor growth over a two-week period in a pilot orthotopic allograft model. Evaluation of single and combination drugs in six human primary vestibular schwannoma cell models revealed the combination was superior to the monotherapies in 3 of 6 VS samples, highlighting inter-tumor variability between patients consistent with observations from clinical trials with other molecular targeted agents. Dasatinib alone performed as well as the combination in the remaining three samples. Preclinically validated combination therapies hold promise for NF2 patients and warrants further study in clinical trials.
Data from Preclinical development of brain permeable ERβ agonist for the treatment of glioblastoma
Authors: Pratap Uday P. , Tidwell Michael , Balinda Henriette U. , Clanton Nicholas A. , Yang Xue , Viswanadhapalli Suryavathi , Sareddy Gangadhara R. , Liang Dong , Xie Huan , Chen Yidong , Lai Zhao , Tekmal Rajeshwar R. , McHardy Stanton F. , Brenner Andrew J. , Vadlamudi Ratna K.
Published: September 2024

Abstract
Glioblastoma (GBM) is the most prevalent and aggressive type of adult brain tumors with low 5-year overall survival rates. Epidemiologic data suggest that estrogen may decrease brain tumor growth, and estrogen receptor beta (ERβ) has been demonstrated to exert anti-tumor functions in GBM. The lack of potent, selective and brain permeable ERβ agonist to promote its anti-tumor action is limiting the therapeutic promise of ERβ. In this study, we discovered that Indanone and tetralone-keto or hydroxyl oximes are a new class of ER agonists. Due to its high activity in ERβ reporter assays, specific binding to ERβ in polar screen assays, and potent growth inhibitory activity in GBM cells, CIDD-0149897 was discovered as a possible hit by screening a library of compounds. CIDD-0149897 is more selective for ERβ than ERα (40-fold). Treatment with CIDD-0149897 markedly reduced GBM cell viability with an IC50 of ~7-15 µM, while having little to no effect on ERβ-KO cells and normal human astrocytes. Further, CIDD-0149897 treatment enhanced expression of known ERβ target genes and promoted apoptosis in established and patient-derived GSC models. Pharmacokinetic studies confirmed that CIDD-0149897 has systemic exposure, and good bioavailability in the brain. Mice tolerated daily intraperitoneal treatment of CIDD-0149897 (50 mg/kg) with a 7-day repeat dosage with no toxicity. Additionally, CIDD-0149897 treatment significantly decreased tumor growth in U251 xenograft model and extended the survival of orthotopic GBM tumor-bearing mice. Collectively, these findings pointed to CIDD-0149897 as a new class of ERβ agonist, offering GBM patients a potential means of improving survival.
Data from Activation of Hepatocyte Growth Factor/MET Signaling as a Mechanism of Acquired Resistance to a Novel YAP1/TEAD Small Molecule Inhibitor
Authors: Moure Casey J. , Vara Brandon , Cheng Mangeng M. , Sondey Christopher , Muise Eric , Park Eunsil , Vela Ramirez Julia Eulalia , Su Dan , D’Souza Shanti , Yan Qingyun , Yeung Charles S. , Zhang Minjia , Mansueto My Sam , Linn Doug , Buchanan Mark , Foti Robert , DiMauro Erin , Long Brian , Simov Vladimir , Barry Evan R.
Published: September 2024

Abstract
Many tumor types harbor alterations in the Hippo pathway, including mesothelioma, where a high percentage of cases are considered YAP1/TEAD dependent. Identification of autopalmitoylation sites in the hydrophobic palmitate pocket of TEADs, which may be necessary for YAP1 protein interactions, has enabled modern drug discovery platforms to generate compounds that allosterically inhibit YAP1/TEAD complex formation and transcriptional activity. We report the discovery and characterization of a novel YAP1/TEAD inhibitor MRK-A from an aryl ether chemical series demonstrating potent and specific inhibition of YAP1/TEAD activity. In vivo, MRK-A showed a favorable tolerability profile in mice and demonstrated pharmacokinetics suitable for twice daily oral dosing in preclinical efficacy studies. Importantly, monotherapeutic targeting of YAP1/TEAD in preclinical models generated regressions in a mesothelioma CDX model; however, rapid resistance to therapy was observed. RNA-sequencing of resistant tumors revealed mRNA expression changes correlated with the resistance state and a marked increase of hepatocyte growth factor (HGF) expression. In vitro, exogenous HGF was able to fully rescue cytostasis induced by MRK-A in mesothelioma cell lines. In addition, co-administration of small molecule inhibitors of the MET receptor tyrosine kinase suppressed the resistance generating effect of HGF on MRK-A induced growth inhibition. In this work, we report the structure and characterization of MRK-A, demonstrating potent and specific inhibition of YAP1/TAZ-TEAD–mediated transcriptional responses, with potential implications for treating malignancies driven by altered Hippo signaling, including factors resulting in acquired drug resistance.
Emerging Tumor-Agnostic Molecular Targets
Authors: Bhamidipati Dedipya , Schram Alison M.
Published: September 2024

Advances in tumor molecular profiling have uncovered shared genomic and proteomic alterations across tumor types that can be exploited therapeutically. A biomarker-driven, disease-agnostic approach to oncology drug development can maximize the reach of novel therapeutics. To date, eight drug–biomarker pairs have been approved for the treatment of patients with advanced solid tumors with specific molecular profiles. Emerging biomarkers with the potential for clinical actionability across tumor types include gene fusions involving NRG1, FGFR1/2/3, BRAF, and ALK and mutations in TP53 Y220C, KRAS G12C, FGFR2/3, and BRAF non-V600 (class II). We explore the growing evidence for clinical actionability of these biomarkers in patients with advanced solid tumors.
Figure S6 from Interdependence of SS18-SSX-driven YAP1 and β-catenin activation in synovial sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: September 2024

Figure S6 shows that the mutual activation of YAP1/TAZ and β-catenin in SySa cells is impeded by knockdown of BAF complex subunits.
Figure S4 from Interdependence of SS18-SSX-driven YAP1 and β-catenin activation in synovial sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: September 2024

Figure S4 shows that induction of hyperactive YAP1/TAZ or β-catenin variants does not alter the other’s protein levels.
Figure S3 from Interdependence of SS18-SSX-driven YAP1 and β-catenin activation in synovial sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: September 2024

Figure S3 shows a reciprocal regulation of YAP1/TAZ-TEAD and β-catenin-TCF in SySa cells via luciferase assays.
Supplementary Figure Legend 1 and Supplementary Table 1 from Non-essential amino acid availability influences proteostasis and breast cancer cell survival during proteotoxic stress
Authors: Sannino Sara , Manuel Allison M. , Shang Chaowei , Wendell Stacy G. , Wipf Peter , Brodsky Jeffrey L.
Published: September 2024

Legend to supplementary figure S1 and Table S1 containing a list of reagents and chemicals used to perform the experiments in the manuscript
Supplementary Table 7 from Disruption of the MYC Super-Enhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , VanCampen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Daniel , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: September 2024

GO Analysis from Regions of Differential MOLM13 H3K27Ac CUT&Tag (6 Hours After Drug Treatment) Pileup at Enhancers and Promoters
Supplementary Table 5 from Disruption of the MYC Super-Enhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , VanCampen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Daniel , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: September 2024

Normalized Read Pileup and Differential Enrichment Clusters of MOLM13 H3K27Ac CUT&Tag (2 Hours After Drug Treatment)
Supplementary Table 3 from Disruption of the MYC Super-Enhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , VanCampen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Daniel , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: September 2024

Transcription Factor Enrichment Analysis of Differentially Downregulated Genes by The Drug Combination Previously Identified as Depleting Genes in a Genome-Wide CRISPR Dropout Screen
Supplementary Table 13 from Disruption of the MYC Super-Enhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , VanCampen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Daniel , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: September 2024

Excess over Bliss of Primary AML Blasts from 72 Patient Samples
Supplementary Table S1, S2 from MACdb: A curated knowledgebase for metabolic associations across human cancers
Authors: Sun Yanling , Zheng Xinchang , Wang Guoliang , Wang Yibo , Chen Xiaoning , Sun Jiani , Xiong Zhuang , Zhang Sisi , Wang Tianyi , Fan Zhuojing , Bu Congfan , Bao Yiming , Zhao Wenming
Published: September 2024

Supplementary Table S1, S2
Supplementary Figure 2 from Critical role of 6-phosphogluconate dehydrogenase in TAp73-mediated cancer cell proliferation
Authors: Qiao Rui , Wei Mengmeng , Chen Hui , Zhang Xianhong , Zhang Jie , Gao Liyang , Ma Haijun , Wang Yujiong , Li Le
Published: September 2024

S2. TAp73 enhances PPP via 6PGD
Figure S6 from Dynamic intestinal stem cell plasticity and lineage remodeling by a nutritional environment relevant to human risk for tumorigenesis
Authors: Choi Jiahn , Zhang Xusheng , Li Wenge , Houston Michele , Peregrina Karina , Dubin Robert , Ye Kenny , Augenlicht Leonard
Published: September 2024

Single cell analyses of cell progeny of the alternate stem cells mobilized by the western diet to maintain the mucosa.
Figure S5 from Dynamic intestinal stem cell plasticity and lineage remodeling by a nutritional environment relevant to human risk for tumorigenesis
Authors: Choi Jiahn , Zhang Xusheng , Li Wenge , Houston Michele , Peregrina Karina , Dubin Robert , Ye Kenny , Augenlicht Leonard
Published: September 2024

Single cell RNAsequencing following 4 days of dietary switch, or then switch back and comparison to pathways altered in stem cells by Ppargc1a genetic inactivation.
Supplementary Figure S2 from Overlaid transcriptome and proteome analyses identify mitotic kinesins as important targets of arylsulfonamide-mediated RBM39 degradation
Authors: Coomar Seemon , Mota Pedro , Penson Alexander , Schwaller Juerg , Abdel-Wahab Omar , Gillingham Dennis
Published: September 2024

Supplementary Figure S2
Supplementary Data from Overlaid transcriptome and proteome analyses identify mitotic kinesins as important targets of arylsulfonamide-mediated RBM39 degradation
Authors: Coomar Seemon , Mota Pedro , Penson Alexander , Schwaller Juerg , Abdel-Wahab Omar , Gillingham Dennis
Published: September 2024

eClip Scores
Supplementary Data Table 1 from Overlaid transcriptome and proteome analyses identify mitotic kinesins as important targets of arylsulfonamide-mediated RBM39 degradation
Authors: Coomar Seemon , Mota Pedro , Penson Alexander , Schwaller Juerg , Abdel-Wahab Omar , Gillingham Dennis
Published: September 2024

Supplementary Data Table 1
Fig. S6 from Absence of either Ripk3 or Mlkl reduces incidence of hepatocellular carcinoma independent of liver fibrosis
Authors: Mohammed Sabira , Thadathil Nidheesh , Ohene-Marfo Phoebe , Tran Albert L. , Van Der Veldt Michael , Georgescu Constantin , Oh Sangphil , Nicklas Evan H. , Wang Dawei , Haritha Nair Hariprasad , Luo Wenyi , Janknecht Ralf , Miller Benjamin F. , Wren Jonathan D. , Freeman Willard M. , Deepa Sathyaseelan S.
Published: September 2024

Fig S6 shows ingenuity pathway analysis for canonical pathways and upstream regulators
Fig. S5 from Absence of either Ripk3 or Mlkl reduces incidence of hepatocellular carcinoma independent of liver fibrosis
Authors: Mohammed Sabira , Thadathil Nidheesh , Ohene-Marfo Phoebe , Tran Albert L. , Van Der Veldt Michael , Georgescu Constantin , Oh Sangphil , Nicklas Evan H. , Wang Dawei , Haritha Nair Hariprasad , Luo Wenyi , Janknecht Ralf , Miller Benjamin F. , Wren Jonathan D. , Freeman Willard M. , Deepa Sathyaseelan S.
Published: September 2024

Figure S5 shows images of liver nodules, transcript levels of AFP
Supplementary Table S6 from Single-Cell Evolutionary Analysis Reveals Drivers of Plasticity and Mediators of Chemoresistance in Small Cell Lung Cancer
Authors: Wollenzien Hannah , Tecleab Yohannes Afeworki A. , Szczepaniak-Sloane Robert , Restaino Anthony , Kareta Michael S.
Published: September 2024

Normalized differentially expressed genes between subclones (related to Figure 5a)
Supplementary Table S4 from Single-Cell Evolutionary Analysis Reveals Drivers of Plasticity and Mediators of Chemoresistance in Small Cell Lung Cancer
Authors: Wollenzien Hannah , Tecleab Yohannes Afeworki A. , Szczepaniak-Sloane Robert , Restaino Anthony , Kareta Michael S.
Published: September 2024

Differential gene expression across NCI-H209 and NCI-H82 cluster (related to Figure 4)
Supplementary Table S3 from Single-Cell Evolutionary Analysis Reveals Drivers of Plasticity and Mediators of Chemoresistance in Small Cell Lung Cancer
Authors: Wollenzien Hannah , Tecleab Yohannes Afeworki A. , Szczepaniak-Sloane Robert , Restaino Anthony , Kareta Michael S.
Published: September 2024

Gene module membership and expression of module 5 (related to Figure 1g)
Supplementary Figure 1 from Oncostatin-M and OSM-Receptor feed-forward activation of MAPK induces separable stem-like and mesenchymal programs
Authors: Polak Kelsey L. , Tamagno Ilaria , Parameswaran Neetha , Smigiel Jacob , Chan E. Ricky , Yuan Xueer , Rios Brenda , Jackson Mark W.
Published: September 2024

S1. OSM induces tumor initiation.
Supplementary Figure 3 from Targeting the ATF6-mediated ER stress response and autophagy blocks integrin-driven prostate cancer progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: September 2024

Figure S3. (A) Representative images of triple IHC staining of Integrin αvβ6 (green), Gal-3 (brown), and Na+/K+-ATPase (red) in normal prostate and tumor tissues from PCa patients with different grades. Deconvoluted images of Integrin αvβ6 are shown on the right; bars, 100 µm. (B) Quantification of Integrin αvβ6 H-score at PM from samples in A. Dunn Test (1964) Kruskal-Wallis multiple comparisons, p-adjusted using Benjamini-Hochberg; ****p<0.0001 and **p<0.01, median ± SD. (C) Quantification of Integrin αvβ6 and Gal-3 colocalization at PM in normal prostate and PCa, grades 2-5. Mann Whitney test; ***p<0.001, mean ± SD.
Supplementary Figure 2 from Targeting the ATF6-mediated ER stress response and autophagy blocks integrin-driven prostate cancer progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: September 2024

Figure S2. (A) Representative images of triple IHC staining of Integrin αvβ5 (green), Gal-3 (red), and E-cadherin (brown) in the normal prostate and tumor tissues from PCa patients with different grades. Deconvoluted images of Integrin αvβ5 are shown on the right; bars, 100 µm. (B) Quantification of Integrin αvβ5 H-score at PM from samples in A. Dunn Test (1964) Kruskal-Wallis multiple comparisons, p-adjusted using Benjamini-Hochberg; ****p<0.0001 and ***p<0.001, median ± SD. (C) Quantification of Integrin αvβ5 and Gal-3 colocalization at PM in normal prostate and PCa, grades 2-5. Kruskal-Wallis test; ***p<0.001, mean ± SD.
Supplementary Figure 10 from Targeting the ATF6-mediated ER stress response and autophagy blocks integrin-driven prostate cancer progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: September 2024

Figure S10. (A) Evaluation of MGAT5-mediated Integrin αv glycosylation in the orthotopic tumor samples. Tissue samples were co-stained with Integrin αv (green) and Cy3 labeled PHA-L lectin (red). Representative Z-stack images were collected by SIM and reconstructed using Imaris for clarity. (B) Mander's colocalization between red and green in the samples from A. Kruskal-Wallis test; n indicates the number of foci counted. For all statistics: median ± SD, ****p<0.0001, ***p<0.001, **p<0.005, *p<0.05. (C) Evaluation of MGAT3-mediated Integrin αv glycosylation in the orthotopic tumor samples. Tissue samples were co-stained with Integrin αv (green) and Cy3 labeled PHA-E lectin (red). Representative Z-stack images were collected by SIM and reconstructed using Imaris for clarity; bars, 3 µm. (D) Mander's colocalization between red and green in the samples from C. Kruskal-Wallis test; n indicates the number of foci counted; mean ± SD, ****p<0.0001, **p<0.01, and *p<0.05.
Movie S3 from Targeting the ATF6-mediated ER stress response and autophagy blocks integrin-driven prostate cancer progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: September 2024

PC-3 cell treated with water, stained for Integrin αv (red), Gal-3 (green), EEA1 (magenta). Areas of 3-color colocalization are highlighted with white. Surfaces were reconstructed by Imaris.
Movie S2 from Targeting the ATF6-mediated ER stress response and autophagy blocks integrin-driven prostate cancer progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: September 2024

PC-3 cell treated with HCQ, stained for Golgi (GRASP65, green) and MGAT3 (red). Surfaces were reconstructed by Imaris.
Supplementary Figure 7 from Continuous administration of anti-VEGFA antibody upregulates PAI-1 secretion from ovarian cancer cells via miR-143-3p downregulation
Authors: Yagi Taro , Sawada Kenjiro , Miyamoto Mayuko , Shimizu Aasa , Oui Yukako , Toda Aska , Nakamura Koji , Kinose Yasuto , Kodama Michiko , Hashimoto Kae , Kimura Tadashi
Published: September 2024

Supplementary Figure 7 shows that the transduction of miR-143-3p did not affect tumor growth in a murine model of ovarian cancer.
Supplementary Figure 6 from Continuous administration of anti-VEGFA antibody upregulates PAI-1 secretion from ovarian cancer cells via miR-143-3p downregulation
Authors: Yagi Taro , Sawada Kenjiro , Miyamoto Mayuko , Shimizu Aasa , Oui Yukako , Toda Aska , Nakamura Koji , Kinose Yasuto , Kodama Michiko , Hashimoto Kae , Kimura Tadashi
Published: September 2024

Supplementary Figure 6 shows that the transduction of miR-143-3p does not attenuate in vitro tube formation in HUVECs incubated with the culture media of SKOV3ip1 cells.
Table S3 from HCK promotes high-grade serous ovarian cancer tumorigenesis through CD44 and NOTCH3 signaling
Authors: Khella Christen A. , Franciosa Lucyann , Rodriguez-Rodriguez Lorna , Rajkarnikar Resha , Mythreye Karthikeyan , Gatza Michael L.
Published: September 2024

Summary of differentially expressed proteins (RPPA analysis) following HCK silencing in CAOV3 cells
Fig S4 from HCK promotes high-grade serous ovarian cancer tumorigenesis through CD44 and NOTCH3 signaling
Authors: Khella Christen A. , Franciosa Lucyann , Rodriguez-Rodriguez Lorna , Rajkarnikar Resha , Mythreye Karthikeyan , Gatza Michael L.
Published: September 2024

The effect of GSIs on NOTCH3 ICD expression in HGSOC cells following HCK overexpression.
Fig S2 from HCK promotes high-grade serous ovarian cancer tumorigenesis through CD44 and NOTCH3 signaling
Authors: Khella Christen A. , Franciosa Lucyann , Rodriguez-Rodriguez Lorna , Rajkarnikar Resha , Mythreye Karthikeyan , Gatza Michael L.
Published: September 2024

The source of elevated HCK signature is not due to a bias in tumor purity or immune infiltration.
Supplementary Figure 3 from Simultaneous targeting of DNA polymerase theta and PARP1 or RAD52 triggers dual synthetic lethality in homologous recombination-deficient leukemia cells
Authors: Sullivan-Reed Katherine , Toma Monika M. , Drzewiecka Malgorzata , Nieborowska-Skorska Margaret , Nejati Reza , Karami Adam , Wasik Mariusz A. , Sliwinski Tomasz , Skorski Tomasz
Published: September 2024

S3. Simultaneous inhibition of Polθ helicase and DNA polymerase
activity exerted synergistic effect against RAD54-/- leukemia cells.
Supplemental Figure 9 from Mitochondrial uncoupling inhibits reductive carboxylation in cancer cells
Authors: Jiang Haowen , He Clifford Jiajun , Li Albert M. , He Bo , Li Yang , Zhou Meng-Ning , Ye Jiangbin
Published: September 2024

S9. ETC inhibition only inhibits proliferation, but not spheroid formation, while Mitochondrial uncoupling inhibits both.
Supplemental Figure 8 from Mitochondrial uncoupling inhibits reductive carboxylation in cancer cells
Authors: Jiang Haowen , He Clifford Jiajun , Li Albert M. , He Bo , Li Yang , Zhou Meng-Ning , Ye Jiangbin
Published: September 2024

S8. Mitochondrial uncoupling inhibits proliferation upon anchorage-independent growth.
Supplemental Figure 6 from Mitochondrial uncoupling inhibits reductive carboxylation in cancer cells
Authors: Jiang Haowen , He Clifford Jiajun , Li Albert M. , He Bo , Li Yang , Zhou Meng-Ning , Ye Jiangbin
Published: September 2024

S6. Mitochondrial uncoupling inhibits reductive carboxylation in ccRCC cells.
Supplemental Figure 3 from Allele-specific gene regulation, phenotypes, and therapeutic vulnerabilities in estrogen receptor alpha mutant endometrial cancer
Authors: Blanchard Zannel , Rush Craig M. , Arnesen Spencer , Vahrenkamp Jeffery M. , Rodriguez Adriana C. , Jarboe Elke A. , Brown Callie , Chang Matthew E.K. , Flory Mark R. , Mohammed Hisham , Modzelewska Katarzyna , Lum David H. , Gertz Jason
Published: September 2024

ER binding is altered by the Y537S and D538G mutations
Supplementary Figure 1 from LncRNA-encoded Micropeptide ACLY‍-‍BP drives lipid deposition and cell proliferation in Clear Cell Renal Cell Carcinoma via maintenance of ACLY acetylation
Authors: Zhang Shenghua , Zhang Zheng , Liu Xiaolong , Deng Yibin , Zheng Jian , Deng Jieqiong , Wang Yirong , Guo Binbin , Li Fanrong , Chen Xiaoyue , Pan Yacheng , Wang Jieyu , Lu Jiachun , Wu Siqi , Guo Qiang , Zhou Yifeng
Published: September 2024

Screening of candidate lncRNAs and biologic characterization of LINC00887
Supplementary Table 2 from Hierarchical phosphorylation of HOXB13 by mTOR dictates its activity and oncogenic function in prostate cancer
Authors: Chen Yonghong , Dufour Catherine R. , Han Lingwei , Li Ting , Xia Hui , Giguere Vincent
Published: September 2024

Supplementary Table 2. RNA-seq analysis of LNCaP mTOR KD cells rescued with mTOR or empty vector (EV) control ± R1881 for 24h.
Supplementary Figure 3 from Hierarchical phosphorylation of HOXB13 by mTOR dictates its activity and oncogenic function in prostate cancer
Authors: Chen Yonghong , Dufour Catherine R. , Han Lingwei , Li Ting , Xia Hui , Giguere Vincent
Published: September 2024

Supplementary Figure 3. SKP2 is an E3 ligase for HOXB13.
Figure S4 from TRIM50 inhibits gastric cancer progression by regulating the ubiquitination and nuclear translocation of JUP
Authors: Hu Jiajia , Huang Runjie , Liang Chengcai , Wang Yingnan , Wang Min , Chen Yanxing , Wu Chenyi , Zhang Jinling , Liu Zekun , Zhao Qi , Liu Zexian , Wang Feng , Yuan Shuqiang
Published: September 2024

Figure S4: The TRIM50 and JUP binding domain predicted by I-TASSER-MTD. Blue indicated TRIM50. Green indicated JUP. Purple highlighted the interaction sites in RING and PRY/SPRY domain.