bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary figure 2 from Characterization of HCC Mouse Models: Towards an Etiology-Oriented Subtyping Approach
Authors: Friemel Juliane , Frick Lukas , Unger Kristian , Egger Michele , Parrotta Rossella , Böge Yannick T. , Adili Arlind , Karin Michael , Luedde Tom , Heikenwalder Mathias , Weber Achim
Published: April 2023

non-tumorous murine livers
Supplementary figure 1 from Characterization of HCC Mouse Models: Towards an Etiology-Oriented Subtyping Approach
Authors: Friemel Juliane , Frick Lukas , Unger Kristian , Egger Michele , Parrotta Rossella , Böge Yannick T. , Adili Arlind , Karin Michael , Luedde Tom , Heikenwalder Mathias , Weber Achim
Published: April 2023

guide to murine tumor analysis
Supplementary Figure S5 from FoxO3a Mediates the Inhibitory Effects of the Antiepileptic Drug Lamotrigine on Breast Cancer Growth
Authors: Pellegrino Michele , Rizza Pietro , Nigro Alessandra , Ceraldi Rosangela , Ricci Elena , Perrotta Ida , Aquila Saveria , Lanzino Marilena , Andò Sebastiano , Morelli Catia , Sisci Diego
Published: April 2023

FoxO3a and Akt phosphorylation in response to LTG treatment.
Figure S4 from PKCϵ Controls Mitotic Progression by Regulating Centrosome Migration and Mitotic Spindle Assembly
Authors: Martini Silvia , Soliman Tanya , Gobbi Giuliana , Mirandola Prisco , Carubbi Cecilia , Masselli Elena , Pozzi Giulia , Parker Peter J. , Vitale Marco
Published: April 2023

Figure S4. PKCe inhibition results in mitotic spindle disorganization in HEL cells and DLD1 PKCe M486A cells.
Figure S2 from PKCϵ Controls Mitotic Progression by Regulating Centrosome Migration and Mitotic Spindle Assembly
Authors: Martini Silvia , Soliman Tanya , Gobbi Giuliana , Mirandola Prisco , Carubbi Cecilia , Masselli Elena , Pozzi Giulia , Parker Peter J. , Vitale Marco
Published: April 2023

This figure show that Ciliobrevin treatment results in mitotic spindle defects, delay of centrosome movement and bending phenotype.
Supplementary Figure S1 from FoxO3a Mediates the Inhibitory Effects of the Antiepileptic Drug Lamotrigine on Breast Cancer Growth
Authors: Pellegrino Michele , Rizza Pietro , Nigro Alessandra , Ceraldi Rosangela , Ricci Elena , Perrotta Ida , Aquila Saveria , Lanzino Marilena , Andò Sebastiano , Morelli Catia , Sisci Diego
Published: April 2023

ERK1/2 phosphorylation in response to LTG treatment.
Supplementary Figures S1-S4 from GPR56 Drives Colorectal Tumor Growth and Promotes Drug Resistance through Upregulation of MDR1 Expression via a RhoA-Mediated Mechanism
Authors: Zhang Sheng , Chatterjee Treena , Godoy Carla , Wu Ling , Liu Qingyun J. , Carmon Kendra S.
Published: April 2023

Figure S1. Effects of loss of LGR5 on GPR56 expression in colon cancer cells. Figure S2. Effects of GPR56 levels on colon cancer cell proliferation, drug resistance, and ABC transporter expression Figure S3. Changes in MDR1 levels and function in colon cancer cells Figure S4. Effects of inhibitors of MDR1 and Rho on colon cancer cell sensitivity to 5-FU
Supplementary Information from Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression
Authors: Fedele Vita , Dai Fangping , Masilamani Anie P. , Heiland Dieter H. , Kling Eva , Gätjens-Sanchez Ana M. , Ferrarese Roberto , Platania Leonardo , Doostkam Soroush , Kim Hyunsoo , Nelander Sven , Weyerbrock Astrid , Prinz Marco , Califano Andrea , Iavarone Antonio , Bredel Markus , Carro Maria S.
Published: April 2023

Supplementary Figure legends and tables.
Supplementary Figure 6 from Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression
Authors: Fedele Vita , Dai Fangping , Masilamani Anie P. , Heiland Dieter H. , Kling Eva , Gätjens-Sanchez Ana M. , Ferrarese Roberto , Platania Leonardo , Doostkam Soroush , Kim Hyunsoo , Nelander Sven , Weyerbrock Astrid , Prinz Marco , Califano Andrea , Iavarone Antonio , Bredel Markus , Carro Maria S.
Published: April 2023

ZBTB18 promoter methylation analysis.
Supplementary Figure 5 from Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression
Authors: Fedele Vita , Dai Fangping , Masilamani Anie P. , Heiland Dieter H. , Kling Eva , Gätjens-Sanchez Ana M. , Ferrarese Roberto , Platania Leonardo , Doostkam Soroush , Kim Hyunsoo , Nelander Sven , Weyerbrock Astrid , Prinz Marco , Califano Andrea , Iavarone Antonio , Bredel Markus , Carro Maria S.
Published: April 2023

Proliferation, migration and invasion assays in BTSC233 and JX6 cells.
Supplementary Table 1 from Inhibition of Ciliogenesis Promotes Hedgehog Signaling, Tumorigenesis, and Metastasis in Breast Cancer
Authors: Hassounah Nadia B. , Nunez Martha , Fordyce Colleen , Roe Denise , Nagle Ray , Bunch Thomas , McDermott Kimberly M.
Published: April 2023

Supplemental Table S1. Descriptive Statistics for Progression-free Survival Times for the Ift88/PyMT+ Tumor Growth Study.
Supplementary Figure 2 from Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression
Authors: Fedele Vita , Dai Fangping , Masilamani Anie P. , Heiland Dieter H. , Kling Eva , Gätjens-Sanchez Ana M. , Ferrarese Roberto , Platania Leonardo , Doostkam Soroush , Kim Hyunsoo , Nelander Sven , Weyerbrock Astrid , Prinz Marco , Califano Andrea , Iavarone Antonio , Bredel Markus , Carro Maria S.
Published: April 2023

GSEA analysis in BTSC233.
Supplementary Figure 1 from Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression
Authors: Fedele Vita , Dai Fangping , Masilamani Anie P. , Heiland Dieter H. , Kling Eva , Gätjens-Sanchez Ana M. , Ferrarese Roberto , Platania Leonardo , Doostkam Soroush , Kim Hyunsoo , Nelander Sven , Weyerbrock Astrid , Prinz Marco , Califano Andrea , Iavarone Antonio , Bredel Markus , Carro Maria S.
Published: April 2023

Characterization of ZBTB18 short band by MS.
Supplementary Data from Mitotic DNA Synthesis Is Differentially Regulated between Cancer and Noncancerous Cells
Authors: Graber-Feesl Cari L. , Pederson Kayla D. , Aney Katherine J. , Shima Naoko
Published: April 2023

S1. Depletion of RAD52 or FANCD2 in WT HCT116 cells phenocopies R52KO or D2KO cells, respectively. S2. Depletion of MCM4 is relatively inefficient in inducing EdU spot formation in HCT116 cells. S3. The formation of Aph- or siORC1-induced EdU spots depends both on RAD52 and FANCD2 in U2OS cells. S4. The formation of EdU spots depends both on RAD52 and FANCD2 in HeLa cells. S5. Depletion of FANCD2 or RAD52 confers similar cell cycle profiles. S6. EdU spots induced by BRCA2 depletion display the characteristics of mitotic DNA synthesis.
Supplementary Figure 2 from Aurora Kinase A Promotes AR Degradation via the E3 Ligase CHIP
Authors: Sarkar Sukumar , Brautigan David L. , Larner James M.
Published: April 2023

CHIP phosphorylation is independent Cdk(s)
Supplementary Table S1 from Targeting CREB Pathway Suppresses Small Cell Lung Cancer
Authors: Xia Yifeng , Zhan Cheng , Feng Mingxiang , Leblanc Mathias , Ke Eugene , Yeddula Narayana , Verma Inder M.
Published: April 2023

Supplementary Table S1. Status of CREB and NF-κB pathway activation in human lung cancers.
Supplementary Materials from Nucleome Analysis Reveals Structure–Function Relationships for Colon Cancer
Authors: Seaman Laura , Chen Haiming , Brown Markus , Wangsa Darawalee , Patterson Geoff , Camps Jordi , Omenn Gilbert S. , Ried Thomas , Rajapakse Indika
Published: April 2023

Figure S1. Copy number based normalization method. Figure S2. Translocation 2-15 at read level. Figure S3. Translocation 3-12 at read level. Figure S4. Translocation 5-6 at read level. Figure S5. Translocation 6-14 at read level. Figure S6. Translocation 19-17 at read level. Figure S7. Translocated chromosome analysis from Hi-C data. Figure S8. Genome-wide Hi-C matrix for 2D-cultured human fibroblast cells. Figure S9. Interchromosomal matrices for translocations. Figure S10. Comparison of normalization methods. Figure S11. Normalization methods on K562 data. Figure S12. Measuring size of chromosome 8 territories. Figure S13. Interactions with the HSR for all samples. Figure S14. Interactions between the HSR and chromosome 2. Figure S15. Read level interactions between chromosomes 17 and 22 indicate there are many different translocations between the different chromosomes.
Figure S1 - S10 from Novel lncRNA LINC00844 Regulates Prostate Cancer Cell Migration and Invasion through AR Signaling
Authors: Lingadahalli Shreyas , Jadhao Sudhir , Sung Ying Ying , Chen Mi , Hu Lingling , Chen Xin , Cheung Edwin
Published: April 2023

S1. The relative expression of KLK3/PSA. S2. Kaplan-Meier analysis of prostate cancer outcome was obtained from GEPIA tool. S3. LNCaP cells with the indicated treatments were seeded in the upper chamber of the Boyden's transwell chamber. S4. LNCaP cells with the indicated treatments were seeded in the upper chamber of the Boyden's transwell chamber which were coated with 1:20 diluted Matrigel. S5. LNCaP cells with the indicated treatments were seeded in the upper chamber of the Boyden's transwell chamber. S6. Snapshots form the AR ChIP-seq showing AR binding to the ARBS. S7. Screenshot from the AR ChIP-seq shows marked reduction in AR binding to the ARBS located at ~ 30kb from the NDRG1 after LINC00844 knock-down in LNCaP cells. S8. LNCaP cells with the indicated treatments were seeded in the upper chamber of the Boyden's transwell chamber. S9. LNCaP cells we co-transfected with the with the indicated siRNA and plasmids and seeded in the upper chamber of the Boyden's transwell chamber. S10. LNCaP cells we co-transfected with the with the indicated siRNA and plasmids cells were harvested and the required amount of cells were used for the migration and invasion assay and rest were lysed for western blot analysis.
Supplementary Methods from Genetic and Epigenetic Characterization of Growth Hormone–Secreting Pituitary Tumors
Authors: Välimäki Niko , Schalin-Jäntti Camilla , Karppinen Atte , Paetau Anders , Kivipelto Leena , Aaltonen Lauri A. , Karhu Auli
Published: April 2023

Supplementary Methods text containing details about mutation status validation of established pituitary adenoma predisposing genes and IHC scoring.
Figure S4 from Loss of Fas Expression and Function Is Coupled with Colon Cancer Resistance to Immune Checkpoint Inhibitor Immunotherapy
Authors: Xiao Wei , Ibrahim Mohammed L. , Redd Priscilla S. , Klement John D. , Lu Chunwan , Yang Dafeng , Savage Natasha M. , Liu Kebin
Published: April 2023

CD133+CD24loFaslo colon cancer stem cell-like cells exhibit increased invasiveness in vitro.
Supplementary data from Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer
Authors: Walter Katherine R. , Goodman Merit L. , Singhal Hari , Hall Jade A. , Li Tianbao , Holloran Sean M. , Trinca Gloria M. , Gibson Katelin A. , Jin Victor X. , Greene Geoffrey L. , Hagan Christy R.
Published: April 2023

Supplemental Figure 1: PR represses ISGs in multiple cell line models. Supplemental Figure 2: ISG repression is PR-dependent. Supplemental Figure 3. ISG repression not observed in PR-negative breast cancer cell lines. Supplemental Figure 4. PR is recruited to ISG enhancers.
Supplementary Figure S4 from HBx-K130M/V131I Promotes Liver Cancer in Transgenic Mice via AKT/FOXO1 Signaling Pathway and Arachidonic Acid Metabolism
Authors: Chiu Amy P. , Tschida Barbara R. , Sham Tung-Ting , Lo Lilian H. , Moriarity Branden S. , Li Xiao-Xiao , Lo Regina C. , Hinton David E. , Rowlands Dewi K. , Chan Chi-On , Mok Daniel K.W. , Largaespada David A. , Warner Nadia , Keng Vincent W.
Published: April 2023

Supplementary Figure S4. Serum metabolite profiles of experimental animals.
Supplementary Figure S2 from HBx-K130M/V131I Promotes Liver Cancer in Transgenic Mice via AKT/FOXO1 Signaling Pathway and Arachidonic Acid Metabolism
Authors: Chiu Amy P. , Tschida Barbara R. , Sham Tung-Ting , Lo Lilian H. , Moriarity Branden S. , Li Xiao-Xiao , Lo Regina C. , Hinton David E. , Rowlands Dewi K. , Chan Chi-On , Mok Daniel K.W. , Largaespada David A. , Warner Nadia , Keng Vincent W.
Published: April 2023

Supplementary Figure S2. IHC staining of FAH, P53, pAKT and CTNNB1.
Supplementary Data Figure 2 from Atorvastatin Decreases HBx-Induced Phospho-Akt in Hepatocytes via P2X Receptors
Authors: Ghalali Aram , Martin-Renedo Javier , Högberg Johan , Stenius Ulla
Published: April 2023

Atorvastatin decreases proliferation in hepatocytes.
Table S1 from Establishment and Genetic Landscape of Precancer Cell Model Systems from the Head and Neck Mucosal Lining
Authors: de Boer D. Vicky , Brink Arjen , Buijze Marijke , Stigter-van Walsum Marijke , Hunter Keith D. , Ylstra Bauke , Bloemena Elisabeth , Leemans C. René , Brakenhoff Ruud H.
Published: April 2023

Overview of the origin of the five visible (erythro)leukoplakia cultures we obtained from others. These five samples were cultured and genetically characterized.
Figure S1 from Establishment and Genetic Landscape of Precancer Cell Model Systems from the Head and Neck Mucosal Lining
Authors: de Boer D. Vicky , Brink Arjen , Buijze Marijke , Stigter-van Walsum Marijke , Hunter Keith D. , Ylstra Bauke , Bloemena Elisabeth , Leemans C. René , Brakenhoff Ruud H.
Published: April 2023

CN profiles of noncancer control UPPP50 revealed a germ-line loss at chromosome 17p. (A) CN profile of the fibroblast culture from UPPP50, with a loss at 17p12. (B) CN profile of the keratinocyte culture from the same sample, showing the same loss at chromosome 17p12. This is the location of the PMP22 gene, known to be affected in HNPP. Both graphs represent the median-normalized log2 transformed read count corresponding to chromosome position.
Supplementary Spreadsheet S1 from p53 Maintains Baseline Expression of Multiple Tumor Suppressor Genes
Authors: Pappas Kyrie , Xu Jia , Zairis Sakellarios , Resnick-Silverman Lois , Abate Francesco , Steinbach Nicole , Ozturk Sait , Saal Lao H. , Su Tao , Cheung Pamela , Schmidt Hank , Aaronson Stuart , Hibshoosh Hanina , Manfredi James , Rabadan Raul , Parsons Ramon
Published: April 2023

Basal p53 ChIP-seq peaks in MCF10A cells (after raw data analysis described in Materials in Methods section) ordered by significance of the peak call. Spreadsheet includes (columns left to right) peak locus (Chromosome, start, end), MACS2 significance, closest relevant gene (genes discussed in paper in red type), and original HOMER gene call (if relevant gene differs from called gene).
Data from HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis
Authors: Zhang Changwen , Yin Chunyang , Wang Lei , Zhang Shuping , Qian Yi , Ma Juan , Zhang Zhihong , Xu Yong , Liu Sijin
Published: April 2023

Abstract
Activation of c-Myc plays a decisive role in the development of many human cancers. As a transcription factor, c-Myc facilitates cell growth and proliferation by directly transcribing a multitude of targets, including rRNAs and ribosome proteins. However, how to elucidate the deregulation of rRNAs and ribosome proteins driven by c-Myc in cancer remains a significant challenge and thus warrants close investigation. In this report, a crucial role for the HSPC111 (NOP16) multiprotein complex in governing ribosomal biogenesis and tumor growth was determined. It was discovered that enhanced HSPC111 expression paralleled the upregulation of c-Myc and was directly regulated by c-Myc in breast cancer cells. Knockdown of HSPC111 dramatically reduced the occurrence of tumorigenesis in vivo, and largely restrained tumor cell growth in vitro and in vivo. In stark contrast, HSPC111 overexpression significantly promoted tumor cell growth. Biochemically, it was demonstrated that RNA 3′-phosphate cyclase (RTCD1/RTCA) interacted with HSPC111, and RTCD1 was involved in the HSPC111 multiprotein complex in regulating rRNA production and ribosomal biogenesis. Moreover, HSPC111 and RTCD1 synergistically modulated cell growth and cellular size through commanding rRNA synthesis and ribosome assembly coupled to protein production. Finally, overall survival analysis revealed that concomitant upregulation of HSPC111 and RTCD1 correlated with the worst prognosis in a breast cancer cohort.

Implications: Inhibition of HSPC111-dependent ribosomal biosynthesis and protein synthesis is a promising therapeutic strategy to diminish breast cancer tumor progression. Mol Cancer Res; 12(4); 583–94. ©2014 AACR.
Data from Tumor Suppressor Functions of miR-133a in Colorectal Cancer
Authors: Dong Yujuan , Zhao Junhong , Wu Chung-Wah , Zhang Lijing , Liu Xiaodong , Kang Wei , Leung Wing-Wah , Zhang Ning , Chan Francis K.L. , Sung Joseph J.Y. , Ng Simon S.M. , Yu Jun
Published: April 2023

Abstract
Dysregulated microRNA (miRNA) expression was profiled through a miRNA array comparison between human colorectal cancer tumors and their adjacent normal tissues. Specifically, using laser capture micro-dissection, miR-133a was shown to be significantly downregulated in primary colorectal cancer specimens compared with matched adjacent normal tissue. Ectopic expression of miR-133a significantly suppressed colorectal cancer cell growth in vitro and in vivo. Cell-cycle analysis revealed that miR-133a induced a G0/G1-phase arrest, concomitant with the upregulation of the key G1-phase regulator p21Cip1. We further revealed that miR-133a markedly increased p53 protein and induced p21Cip1 transcription. Studies in silico revealed that the 3′UTR of the ring finger and FYVE-like domain containing E3-ubiquitin protein ligase (RFFL), which regulates p53 protein, contains an evolutionarily conserved miR-133a binding site. miR-133a repressed RFFL-3′UTR reporter activity and reduced RFFL protein levels, indicating that miR-133a directly bound to RFFL mRNA and inhibited RFFL translation. Moreover, miR-133a sensitized colon cancer cells to doxorubicin and oxaliplatin by enhancing apoptosis and inhibiting cell proliferation. These data add weight to the significance of miR-133a in the development of CRC.

Implications: miR-133a serves as a potential tumor suppressor upstream of p53 in colorectal cancer and may sensitize cells to therapeutics. Mol Cancer Res; 11(9); 1051–60. ©2013 AACR.
Data from Balanced Tiam1-Rac1 and RhoA Drives Proliferation and Invasion of Pancreatic Cancer Cells
Authors: Guo Xingjun , Wang Min , Jiang Jianxin , Xie Chengchen , Peng Feng , Li Xu , Tian Rui , Qin Renyi
Published: April 2023

Abstract
Tiam1 is a rac1-specific guanine nucleotide exchange factor, and Tiam1-rac1 is involved in a number of cellular processes. Rac1 and RhoA act as molecular switches that cycle between GTP- and GDP-bound states to balance the activities of rac1 and RhoA. The downregulation of rac1 activity leads to upregulation of RhoA activity, which promotes invasion and migration of pancreatic cancers cells. At present, however, the role of Tiam1-rac1 and RhoA in pancreatic cancers is not fully understood. We found that Tiam1 was upregulated in pancreatic cancers and was significantly expressed in tumors without lymph node involvement or distant metastasis compared with cancers where there was involvement. Although Tiam1-rac1 signaling promoted pancreatic cancer cell proliferation and tumor growth via the Wnt signaling pathway in vitro and in vivo, inhibiting Tiam1-rac1 signaling did not prolong the overall survival time in vivo. This provided evidence that there was a balance between rac1 and RhoA activities in pancreatic cancers. Furthermore, only the combined inhibition of Tiam1-rac1 and RhoA had a beneficial effect on the growth of pancreatic cancers in vivo. Taken together, these results suggest that the progression of pancreatic tumors is partially controlled by the balance between Tiam1-rac1 and RhoA. Mol Cancer Res; 11(3); 230–9. ©2012 AACR.
Data from PTP1B Contributes to Calreticulin-Induced Metastatic Phenotypes in Esophageal Squamous Cell Carcinoma
Authors: Wang Xiao-Min , Shang Li , Zhang Yu , Hao Jia-Jie , Shi Feng , Luo Wei , Zhang Tong-Tong , Wang Bo-Shi , Yang Yang , Liu Zhi-Hua , Zhan Qi-Min , Wang Ming-Rong
Published: April 2023

Abstract
Calreticulin (CRT) is a Ca2+-binding chaperone protein that alters cellular Ca2+-homeostasis in the endoplasmic reticulum (ER). Previously it was shown that CRT was overexpressed in esophageal squamous cell carcinoma (ESCC), and elevated CRT expression promoted the migration and invasion of ESCC cells. In the present study, the mechanisms underlying the role of CRT in esophageal carcinoma progression were investigated. Critically, depletion of CRT or protein-tyrosine phosphatase 1B (PTP1B) reduced ESCC cell migration and metastasis to the lung, whereas restoration of PTP1B protein levels rescued cell migration in CRT-silenced cells. Knockdown of CRT decreased PTP1B protein expression by reducing phosphorylation at the Y694 site of STAT5A, whereas knockdown of PTP1B reduced ERK1/2 phosphorylation at T204. Immunohistochemical analysis of CRT and PTP1B expression in ESCC patient tissues was strongly correlated. Importantly, PTP1B expression was associated with poor survival in patients with CRT overexpression. Overall, these data indicate a novel signaling pathway connecting CRT, STAT5A, PTP1B, and ERK1/2 in the regulation of ESCC cell migration.

Implications: These findings suggest that PTP1B is a downstream effector of CRT signaling, promotes tumor progression, and can potentially be used as a new drug target for ESCC. Mol Cancer Res; 11(9); 986–94. ©2013 AACR.
Data from Dual Inhibition of PI3K and mTOR Mitigates Compensatory AKT Activation and Improves Tamoxifen Response in Breast Cancer
Authors: Chen Xiaosong , Zhao Meizhong , Hao Mingang , Sun Xueqing , Wang Jinglong , Mao Yan , Zu Lidong , Liu Junjun , Shen Yandong , Wang Jianhua , Shen Kunwei
Published: April 2023

Abstract
Everolimus, an mTOR inhibitor, showed great clinical efficacy in combination with tamoxifen, letrozole, or exemestane for the treatment of estrogen receptor-positive (ER+) breast cancer. However, its antitumor activity was shown to be compromised by a compensatory process involving AKT activation. Here, it was determined whether combining an additional PI3K inhibitor can reverse this phenomenon and improve treatment efficacy. In breast cancer cells (MCF-7 and BT474), everolimus inhibited the mTOR downstream activity by limiting phosphorylation of p70S6K and 4EBP1, which resulted in p-Ser473-AKT activation. However, addition of a LY294002, a PI3K inhibitor, to tamoxifen and everolimus treatment improved the antitumor effect compared with tamoxifen alone or the other two agents in combination. Moreover, LY294002 suppressed the activity of the PI3K/AKT/mTOR axis and mitigated the p-Ser473-AKT activation feedback loop in both cell lines. Critically, this combination scheme also significantly inhibited the expression of HIF-1a, an angiogenesis marker, under hypoxic conditions and reduced blood vessel sprout formation in vitro. Finally, it was shown that the three-agent cocktail had the greatest efficacy in inhibiting MCF-7 xenograft tumor growth and angiogenesis. Taken together, these results suggest that inhibition of PI3K and mTOR may further improve therapy in ER+ breast cancer cells.

Implications: Combinatorial inhibition of the PI3K/AKT/mTOR signaling axis may enhance endocrine-based therapy in breast cancer. Mol Cancer Res; 11(10); 1269–78. ©2013 AACR.
Data from Human Lung Epithelial Cells Progressed to Malignancy through Specific Oncogenic Manipulations
Authors: Sato Mitsuo , Larsen Jill E. , Lee Woochang , Sun Han , Shames David S. , Dalvi Maithili P. , Ramirez Ruben D. , Tang Hao , DiMaio John Michael , Gao Boning , Xie Yang , Wistuba Ignacio I. , Gazdar Adi F. , Shay Jerry W. , Minna John D.
Published: April 2023

Abstract
We used CDK4/hTERT–immortalized normal human bronchial epithelial cells (HBEC) from several individuals to study lung cancer pathogenesis by introducing combinations of common lung cancer oncogenic changes (p53, KRAS, and MYC) and followed the stepwise transformation of HBECs to full malignancy. This model showed that: (i) the combination of five genetic alterations (CDK4, hTERT, sh-p53, KRASV12, and c-MYC) is sufficient for full tumorigenic conversion of HBECs; (ii) genetically identical clones of transformed HBECs exhibit pronounced differences in tumor growth, histology, and differentiation; (iii) HBECs from different individuals vary in their sensitivity to transformation by these oncogenic manipulations; (iv) high levels of KRASV12 are required for full malignant transformation of HBECs, however, prior loss of p53 function is required to prevent oncogene-induced senescence; (v) overexpression of c-MYC greatly enhances malignancy but only in the context of sh-p53+KRASV12; (vi) growth of parental HBECs in serum-containing medium induces differentiation, whereas growth of oncogenically manipulated HBECs in serum increases in vivo tumorigenicity, decreases tumor latency, produces more undifferentiated tumors, and induces epithelial-to-mesenchymal transition (EMT); (vii) oncogenic transformation of HBECs leads to increased sensitivity to standard chemotherapy doublets; (viii) an mRNA signature derived by comparing tumorigenic versus nontumorigenic clones was predictive of outcome in patients with lung cancer. Collectively, our findings show that this HBEC model system can be used to study the effect of oncogenic mutations, their expression levels, and serum-derived environmental effects in malignant transformation, while also providing clinically translatable applications such as development of prognostic signatures and drug response phenotypes.

Visual Overview: http://mcr.aacrjournals.org/content/11/6/638/F1.large.jpg.

Mol Cancer Res; 11(6); 638–50. ©2013 AACR.
Data from FoxM1 is Overexpressed in Helicobacter pylori–Induced Gastric Carcinogenesis and Is Negatively Regulated by miR-370
Authors: Feng Yimin , Wang Lixiang , Zeng Jiping , Shen Li , Liang Xiuming , Yu Han , Liu Shili , Liu Zhifang , Sun Yundong , Li Wenjuan , Chen Chunyan , Jia Jihui
Published: April 2023

Abstract
Helicobacter pylori (H. pylori) infections are strongly implicated in human gastric mucosa–associated diseases. Forkhead box M1 (FoxM1), a key positive regulator of cell proliferation, is overexpressed in gastric cancer. MicroRNAs are important post-transcriptional regulators of gene expression. In this study, the effects of H. pylori infection on FoxM1 expression and possible mechanisms of carcinogenesis were explored. The expression of FoxM1 was gradually increased in human gastric specimens from inflammation to cancer. FoxM1 upregulation was time- and concentration-dependent in gastric epithelial-derived cell lines infected with H. pylori. CagA, a key virulence factor of H. pylori, was associated with increased FoxM1 expression. H. pylori and CagA inhibited the expression of p27Kip1 (CDKN1B) and promoted cell proliferation by upregulating FoxM1. The expression of miR-370 was decreased in human gastritis and gastric cancer. FoxM1 was directly downregulated by miR-370 in gastric cell lines. H. pylori and CagA inhibited miR-370 expression, which led to overexpression of FoxM1 and cell proliferation. Furthermore, the overexpression of FoxM1 and reduced expression of miR-370 was confirmed in H. pylori–infected C57BL/6J mice. H. pylori infection and CagA upregulated FoxM1 expression, dependent on miR-370, altered the expression of p27Kip1, and promoted proliferation in gastric cells.

Implications: These findings delineate the mechanisms governing FoxM1 regulation and the role of H. pylori in the process of gastric carcinogenesis. Mol Cancer Res; 11(8); 834–44. ©2013 AACR.
Data from Comprehensive Molecular Profiling of Olfactory Neuroblastoma Identifies Potentially Targetable FGFR3 Amplifications
Authors: Lazo de la Vega Lorena , McHugh Jonathan B. , Cani Andi K. , Kunder Komal , Walocko Frances M. , Liu Chia-Jen , Hovelson Daniel H. , Robinson Dan , Chinnaiyan Arul M. , Tomlins Scott A. , Harms Paul W.
Published: April 2023

Abstract
Olfactory neuroblastomas (ONBs), also known as esthesioneuroblastomas, are malignant round-cell tumors that represent up to 5% of sinonasal malignancies. Despite their aggressive course, molecular studies of ONBs have been limited, and targeted therapies are lacking. To identify potential oncogenic drivers and targetable pathways in ONBs, we characterized 20 ONBs, including archived ONBs profiled by targeted, multiplexed PCR (mxPCR)–based DNA next-generation sequencing (NGS) of the coding sequence of over 400 cancer-relevant genes (n = 16), mxPCR-based RNA NGS of 108 target genes (n = 15), and 2 ONBs profiled by comprehensive hybrid-capture–based clinical grade NGS of >1,500 genes. Somatic mutations were infrequent in our cohort, with 7 prioritized nonsynonymous mutations in 5 of 18 (28%) ONBs, and no genes were recurrently mutated. We detected arm/chromosome-level copy-number alterations in all tumors, most frequently gains involving all or part of chromosome 20, chromosome 5, and chromosome 11. Recurrent focal amplifications, often but not exclusively in the context of arm-level gains, included CCND1 [n = 4/18 (22%) tumors] and the targetable receptor tyrosine kinase FGFR3 [n = 5/18 (28%) tumors]. Targeted RNA NGS confirmed high expression of FGFR3 in ONB (at levels equivalent to bladder cancer), with the highest expression observed in FGFR3-amplified ONB cases. Importantly, our findings suggest that FGFR3 may be a therapeutic target in a subset of these aggressive tumors.

Implications: ONBs harbor recurrent chromosomal copy-number changes, including FGFR3 amplification associated with overexpression. Hence, FGFR3 may represent a novel therapeutic target in these tumors. Mol Cancer Res; 15(11); 1551–7. ©2017 AACR.
Data from miR-122-5p Expression and Secretion in Melanoma Cells Is Amplified by the LPAR3 SH3–Binding Domain to Regulate Wnt1
Authors: Byrnes Charnel C. , Jia Wei , Alshamrani Ali A. , Kuppa Sudeepti S. , Murph Mandi M.
Published: April 2023

Abstract
The lysophosphatidic acid receptor-3 (LPAR3) is a G protein–coupled receptor that mediates viability among malignant cells and aggressiveness among certain tumors. The study's objective was to determine the interplay between LPAR3 and miRNAs to impact key cellular signaling pathways. Using SK-Mel-2 and SK-Mel-5 melanoma cells, wild-type and mutated receptors were stably expressed to explore molecular mechanisms. LPAR3 signaling induced miR-122-5p intracellularly and subsequently its inclusion into exosomes. This amplification resulted in less abundant Wnt1, maintenance of GSK3 inactivation and to a lesser extent, partial degradation of β-catenin. The surge in miR-122-5p and reduction in Wnt1 originated from signaling at the Src homology 3 (SH3) ligand–binding motif within the third intracellular loop of LPAR3, because mutant receptors did not increase miR-122-5p and had a weakened capacity to reduce Wnt1. In addition, a key mediator of melanoma survival signaling, the peroxisome proliferator-activated receptor gamma coactivator 1-α (PPARGC1A/PGC1), was involved in miR-122-5p transcription. In conclusion, this study highlights the powerful role miRNAs have in fine-tuning specific G protein–coupled receptor-mediated signaling events by altering the transcription of signaling transduction pathway components. This study also identifies that LPAR3 increases miR-122-5p expression, which occurs mechanistically through the SH3 domain and helps explain why miR-122-5p increases are detected in cancer patient serum.
Implications:
LPAR3 is partially responsible for the production and secretion of miR-122-5p, found in the serum of a wide variety of patients with cancer.
Data from Combinations of Tyrosine Kinase Inhibitor and ERAD Inhibitor Promote Oxidative Stress–Induced Apoptosis through ATF4 and KLF9 in Medullary Thyroid Cancer
Authors: Bagheri-Yarmand Rozita , Sinha Krishna M. , Li Ling , Lu Yue , Cote Gilbert J. , Sherman Steven I. , Gagel Robert F.
Published: April 2023

Abstract
Medullary thyroid carcinoma (MTC) originates from the C cells of the thyroid gland, which secrete calcitonin. Lymph node and distant metastases are frequently present at diagnosis. Activating mutations of RET, a driver oncogene in MTC that encodes a tyrosine kinase receptor, prevents apoptosis through inhibition of ATF4, a key transcriptional regulator of endoplasmic reticulum (ER) stress. We hypothesized that the combination of a tyrosine kinase inhibitor (TKI) and an ATF4 inducer promotes cell death by triggering catastrophic oxidative stress and apoptotic cell death. Here, we report that the ER-associated protein degradation (ERAD) inhibitor eeyarestatin sensitized MTC cells to the TKIs, sunitinib and vandetanib, thereby leading to synergistic upregulation of ATF4 expression, accumulation of reactive oxygen species, and subsequent cell death. Genome-wide analysis of ATF4 interaction sites by chromatin immunoprecipitation (ChIP) sequencing revealed that among ATF4 target genes was KLF9 (Kruppel-like factor 9), which induces MTC apoptosis. ChIP assays revealed that ATF4 occupancy at the KLF9 promoter was increased in MTC cells treated with eeyarestatin or vandetanib alone and was further enhanced in cells treated with both drugs, leading to increased KLF9 transcription. Depletion of ATF4 by shRNA led to downregulation of KLF9 expression and prevented oxidative stress–induced cell death. Furthermore, we identified ATF4 target genes (LZTFL1, MKNK2, and SIAH1 with known tumor suppressor function) that were synergistically upregulated with the combination of TKI and ERAD inhibitor.
Implications:
These findings reveal a combination therapy that induces reactive oxygen species–dependent catastrophic cell death through induction of ATF4 and KLF9 transcriptional activity.
Data from Endothelial Cells Promote Colorectal Cancer Cell Survival by Activating the HER3-AKT Pathway in a Paracrine Fashion
Authors: Wang Rui , Bhattacharya Rajat , Ye Xiangcang , Fan Fan , Boulbes Delphine R. , Ellis Lee M.
Published: April 2023

Abstract
The regulation of colorectal cancer cell survival pathways remains to be elucidated. Previously, it was demonstrated that endothelial cells (EC) from the liver (liver parenchymal ECs or LPEC), the most common site of colorectal cancer metastases, secrete soluble factors in the conditioned medium (CM) that, in turn, increase the cancer stem cell phenotype in colorectal cancer cells. However, the paracrine effects of LPECs on other colorectal cancer cellular functions have not been investigated. Here, results showed that CM from LPECs increased cell growth and chemoresistance by activating AKT in colorectal cancer cells in vitro. Using an unbiased receptor tyrosine kinase array, it was determined that human epidermal growth factor receptor 3 (ERBB3/HER3) was activated by CM from LPECs, and it mediated AKT activation, cell growth, and chemoresistance in colorectal cancer cells. Inhibition of HER3, either by an inhibitor AZD8931 or an antibody MM-121, blocked LPEC-induced HER3-AKT activation and cell survival in colorectal cancer cells. In addition, CM from LPECs increased in vivo tumor growth in a xenograft mouse model. Furthermore, inhibiting HER3 with AZD8931 significantly blocked tumor growth induced by EC CM. These results demonstrated a paracrine role of liver ECs in promoting cell growth and chemoresistance via activating HER3-AKT in colorectal cancer cells.
Implications:
This study suggested a potential of treating patients with metastatic colorectal cancer with HER3 antibodies/inhibitors that are currently being assessed in clinical trials for various cancer types.
Data from Pharmacologic Ascorbate Primes Pancreatic Cancer Cells for Death by Rewiring Cellular Energetics and Inducing DNA Damage
Authors: Buranasudja Visarut , Doskey Claire M. , Gibson Adrienne R. , Wagner Brett A. , Du Juan , Gordon David J. , Koppenhafer Stacia L. , Cullen Joseph J. , Buettner Garry R.
Published: April 2023

Abstract
The clinical potential of pharmacologic ascorbate (P-AscH−; intravenous delivery achieving mmol/L concentrations in blood) as an adjuvant in cancer therapy is being reevaluated. At mmol/L concentrations, P-AscH− is thought to exhibit anticancer activity via generation of a flux of H2O2 in tumors, which leads to oxidative distress. Here, we use cell culture models of pancreatic cancer to examine the effects of P-AscH− on DNA damage, and downstream consequences, including changes in bioenergetics. We have found that the high flux of H2O2 produced by P-AscH− induces DNA damage. In response to this DNA damage, we observed that PARP1 is hyperactivated. Using our unique absolute quantitation, we found that P-AscH− mediated the overactivation of PARP1, which results in consumption of NAD+, and subsequently depletion of ATP leading to mitotic cell death. We have also found that Chk1 plays a major role in the maintenance of genomic integrity following treatment with P-AscH−. Hyperactivation of PARP1 and DNA repair are ATP-consuming processes. Using a Seahorse XF96 analyzer, we demonstrated that the severe decrease in ATP after challenging with P-AscH− is because of increased demand, not changes in the rate of production. Genetic deletion and pharmacologic inhibition of PARP1 preserved both NAD+ and ATP; however, the toxicity of P-AscH− remained. These data indicate that disruption of bioenergetics is a secondary factor in the toxicity of P-AscH−; damage to DNA appears to be the primary factor.
Implications:
Efforts to leverage P-AscH− in cancer therapy should first focus on DNA damage.
Data from Molecular Effects of Stromal-Selective Targeting by uPAR-Retargeted Oncolytic Virus in Breast Cancer
Authors: Jing Yuqi , Chavez Valery , Ban Yuguang , Acquavella Nicolas , El-Ashry Doraya , Pronin Alexey , Chen Xi , Merchan Jaime R.
Published: April 2023

Abstract
The tumor microenvironment (TME) is a relevant target for novel biological therapies. MV-m-uPA and MV-h-uPA are fully retargeted, species-specific, oncolytic measles viruses (MV) directed against murine or human urokinase receptor (PLAUR/uPAR), expressed in tumor and stromal cells. The effects of stromal-selective targeting by uPAR-retargeted MVs were investigated. In vitro infection, virus-induced GFP expression, and cytotoxicity by MV-h-uPA and MV-m-uPA were demonstrated in human and murine cancer cells and cancer-associated fibroblasts in a species-specific manner. In a murine fibroblast/human breast cancer 3D coculture model, selective fibroblast targeting by MV-m-uPA inhibited breast cancer cell growth. Systemic administration of murine-specific MV-m-uPA in mice bearing human MDA-MB-231 xenografts was associated with a significant delay in tumor progression and improved survival compared with controls. Experiments comparing tumor (MV-h-uPA) versus stromal (MV-m-uPA) versus combined virus targeting showed that tumor and stromal targeting was associated with improved tumor control over the other groups. Correlative studies confirmed in vivo viral targeting of tumor stroma by MV-m-uPA, increased apoptosis, and virus-induced differential regulation of murine stromal genes associated with inflammatory, angiogenesis, and survival pathways, as well as indirect regulation of human cancer pathways, indicating viral-induced modulation of tumor–stroma interactions. These data demonstrate the feasibility of stromal-selective targeting by an oncolytic MV, virus-induced modulation of tumor–stroma pathways, and subsequent tumor growth delay. These findings further validate the critical role of stromal uPAR in cancer progression and the potential of oncolytic viruses as antistromal agents.

Implications: The current report demonstrates for the first time the biological, in vitro, and in vivo antitumor and molecular effects of stromal selective targeting by an oncolytic virus. Mol Cancer Res; 15(10); 1410–20. ©2017 AACR.
Data from Loss of Fas Expression and Function Is Coupled with Colon Cancer Resistance to Immune Checkpoint Inhibitor Immunotherapy
Authors: Xiao Wei , Ibrahim Mohammed L. , Redd Priscilla S. , Klement John D. , Lu Chunwan , Yang Dafeng , Savage Natasha M. , Liu Kebin
Published: April 2023

Abstract
Despite the remarkable efficacy of immune checkpoint inhibitor (ICI) immunotherapy in various types of human cancers, colon cancer, except for the approximately 4% microsatellite-instable (MSI) colon cancer, does not respond to ICI immunotherapy. ICI acts through activating CTLs that use the Fas–FasL pathway as one of the two effector mechanisms to suppress tumor. Cancer stem cells are often associated with resistance to therapy including immunotherapy, but the functions of Fas in colon cancer apoptosis and colon cancer stem cells are currently conflicting and highly debated. We report here that decreased Fas expression is coupled with a subset of CD133+CD24lo colon cancer cells in vitro and in vivo. Consistent of the lower Fas expression level, this subset of CD133+CD24loFaslo colon cancer cells exhibits decreased sensitivity to FasL-induced apoptosis. Furthermore, FasL selectively enriches CD133+CD24loFaslo colon cancer cells. CD133+CD24loFaslo colon cancer cells exhibit increased lung colonization potential in experimental metastatic mouse models and decreased sensitivity to tumor-specific CTL adoptive transfer and ICI immunotherapies. Interestingly, FasL challenge selectively enriched this subset of colon cancer cells in microsatellite-stable (MSS) but not in the MSI human colon cancer cell lines. Consistent with the downregulation of Fas expression in CD133+CD24lo cells, lower Fas expression level is significantly correlated with decreased survival in patients with human colon cancer.
Implications:
Our data determine that CD133+CD24loFaslo colon cancer cells are capable to evade Fas-FasL cytotoxicity of tumor-reactive CTLs and targeting this subset of colon cancer cells is potentially an effective approach to suppress colon cancer immune evasion.
Data from Lysine-Specific Demethylase 1 Mediates AKT Activity and Promotes Epithelial-to-Mesenchymal Transition in PIK3CA-Mutant Colorectal Cancer
Authors: Miller Samuel A. , Policastro Robert A. , Savant Sudha S. , Sriramkumar Shruthi , Ding Ning , Lu Xiaoyu , Mohammad Helai P. , Cao Sha , Kalin Jay H. , Cole Philip A. , Zentner Gabriel E. , O'Hagan Heather M.
Published: April 2023

Abstract
Activation of the epithelial-to-mesenchymal transition (EMT) program is a critical mechanism for initiating cancer progression and migration. Colorectal cancers contain many genetic and epigenetic alterations that can contribute to EMT. Mutations activating the PI3K/AKT signaling pathway are observed in >40% of patients with colorectal cancer contributing to increased invasion and metastasis. Little is known about how oncogenic signaling pathways such as PI3K/AKT synergize with chromatin modifiers to activate the EMT program. Lysine-specific demethylase 1 (LSD1) is a chromatin-modifying enzyme that is overexpressed in colorectal cancer and enhances cell migration. In this study, we determine that LSD1 expression is significantly elevated in patients with colorectal cancer with mutation of the catalytic subunit of PI3K, PIK3CA, compared with patients with colorectal cancer with WT PIK3CA. LSD1 enhances activation of the AKT kinase in colorectal cancer cells through a noncatalytic mechanism, acting as a scaffolding protein for the transcription-repressing CoREST complex. In addition, growth of PIK3CA-mutant colorectal cancer cells is uniquely dependent on LSD1. Knockdown or CRISPR knockout of LSD1 blocks AKT-mediated stabilization of the EMT-promoting transcription factor Snail and effectively blocks AKT-mediated EMT and migration. Overall, we uniquely demonstrate that LSD1 mediates AKT activation in response to growth factors and oxidative stress, and LSD1-regulated AKT activity promotes EMT-like characteristics in a subset of PIK3CA-mutant cells.
Implications:
Our data support the hypothesis that inhibitors targeting the CoREST complex may be clinically effective in patients with colorectal cancer harboring PIK3CA mutations.
Data from 5-Azacytidine Transiently Restores Dysregulated Erythroid Differentiation Gene Expression in TET2-Deficient Erythroleukemia Cells
Authors: Reilly Brian M. , Luger Timothy , Park Soo , Lio Chan-Wang Jerry , González-Avalos Edahí , Wheeler Emily C. , Lee Minjung , Williamson Laura , Tanaka Tiffany , Diep Dinh , Zhang Kun , Huang Yun , Rao Anjana , Bejar Rafael
Published: April 2023

Abstract
DNA methyltransferase inhibitors (DNMTI) like 5-Azacytidine (5-Aza) are the only disease-modifying drugs approved for the treatment of higher-risk myelodysplastic syndromes (MDS), however less than 50% of patients respond, and there are no predictors of response with clinical utility. Somatic mutations in the DNA methylation regulating gene tet-methylcytosine dioxygenase 2 (TET2) are associated with response to DNMTIs, however the mechanisms responsible for this association remain unknown. Using bisulfite padlock probes, mRNA sequencing, and hydroxymethylcytosine pull-down sequencing at several time points throughout 5-Aza treatment, we show that TET2 loss particularly influences DNA methylation (5mC) and hydroxymethylation (5hmC) patterns at erythroid gene enhancers and is associated with downregulation of erythroid gene expression in the human erythroleukemia cell line TF-1. 5-Aza disproportionately induces expression of these down-regulated genes in TET2KO cells and this effect is related to dynamic 5mC changes at erythroid gene enhancers after 5-Aza exposure. We identified differences in remethylation kinetics after 5-Aza exposure for several types of genomic regulatory elements, with distal enhancers exhibiting longer-lasting 5mC changes than other regions. This work highlights the role of 5mC and 5hmC dynamics at distal enhancers in regulating the expression of differentiation-associated gene signatures, and sheds light on how 5-Aza may be more effective in patients harboring TET2 mutations.
Implications:
TET2 loss in erythroleukemia cells induces hypermethylation and impaired expression of erythroid differentiation genes which can be specifically counteracted by 5-Azacytidine, providing a potential mechanism for the increased efficacy of 5-Aza in TET2-mutant patients with MDS.
Visual Overview:
http://mcr.aacrjournals.org/content/molcanres/19/3/451/F1.large.jpg.
Data from Chemical Screen Identifies Diverse and Novel Histone Deacetylase Inhibitors as Repressors of NUT Function: Implications for NUT Carcinoma Pathogenesis and Treatment
Authors: Shiota Hitoshi , Alekseyenko Artyom A. , Wang Zhipeng A. , Filic Ivona , Knox Tatiana M. , Luong Nhi M. , Huang Yeying , Scott David A. , Jones Kristen L. , Gokhale Prafulla C. , Lemieux Madeleine E. , Cole Philip A. , Kuroda Mitzi I. , French Christopher A.
Published: April 2023

Abstract
NUT carcinoma (NC), characterized most commonly by the BRD4-NUTM1 fusion, is a rare, aggressive variant of squamous carcinoma with no effective treatment. BRD4-NUT drives growth and maintains the poorly differentiated state of NC by activating pro-growth genes such as MYC, through the formation of massive, hyperacetylated, superenhancer-like domains termed megadomains. BRD4-NUT–mediated hyperacetylation of chromatin is facilitated by the chromatin-targeting tandem bromodomains of BRD4, combined with NUT, which recruits the histone acetyltransferase, p300. Here, we developed a high-throughput small-molecule screen to identify inhibitors of transcriptional activation by NUT. In this dCAS9-based GFP-reporter assay, the strongest hits were diverse histone deacetylase (HDAC) inhibitors. Two structurally unrelated HDAC inhibitors, panobinostat and the novel compound, IRBM6, both repressed growth and induced differentiation of NC cells in proportion to their inhibition of NUT transcriptional activity. These two compounds repressed transcription of megadomain-associated oncogenic genes, such as MYC and SOX2, while upregulating pro-differentiation, non-megadomain–associated genes, including JUN, FOS, and key cell-cycle regulators, such as CDKN1A. The transcriptional changes correlate with depletion of BRD4-NUT from megadomains, and redistribution of the p300/CBP-associated chromatin acetylation mark, H3K27ac, away from megadomains toward regular enhancer regions previously populated by H3K27ac. In NC xenograft models, we demonstrated that suppression of tumor growth by panobinostat was comparable with that of bromodomain inhibition, and when combined they improved both survival and growth suppression.
Implications:
The findings provide mechanistic and preclinical rationale for the use of HDAC inhibitors, alone or combined with other agents, in the treatment of NUT carcinoma.