bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Tables 1-5 and Supplementary Figures 1-8 from Aggressive B-cell Lymphoma with MYC/TP53 Dual Alterations Displays Distinct Clinicopathobiological Features and Response to Novel Targeted Agents
Authors: Deng Manman , Xu-Monette Zijun Y. , Pham Lan V. , Wang Xudong , Tzankov Alexandar , Fang Xiaosheng , Zhu Feng , Visco Carlo , Bhagat Govind , Dybkaer Karen , Chiu April , Tam Wayne , Zu Youli , Hsi Eric D. , You Hua , Huh Jooryung , Ponzoni Maurilio , Ferreri Andrés J.M. , Møller Michael B. , Parsons Benjamin M. , Hagemeister Fredrick , van Krieken J. Han , Piris Miguel A. , Winter Jane N. , Li Yong , Xu Bing , Liu Phillip , Young Ken H.
Published: April 2023

Supplementary Table S1. Clinicopathologic characteristics of patients with de novo DLBCL with dual MYC/TP53 aberrations Supplementary Table S2. Frequency of single or dual abnormal Myc protein, p53 protein, BCL2 protein, MYC gene, and TP53 gene in the studied patients with DLBCL treated with R-CHOP Supplementary Table S3. Prognostic factors by univariate analysis and multivariate analysis in DLBCL Supplementary Table S4. Gene expression signatures identified by comparing DLBCL patients with concurrent MYC-R Mut-TP53 or Mychigh Mut-TP53 alterations (double-positive) with DLBCL patients withSupplementary Table S5. Molecular, genetic and phenotypic status of 8 DLBCL/HGBCL cell lines by targeted next-generation sequencing, fluorescence in situ hybridization (FISH), and immunohistochemistry analysis none or the alterations (double-negative) Supplementary Figure S1. Morphologic and immunophenotypic features of DLBCL with MYC rearrangement (MYC-R) and TP53 mutation (Mut-TP53) dual-alterations and highgrade B-cell lymphoma (HGBCL) with MYC/BCL2 double-hit (DH) in representative patients. Supplementary Figure S2. Prognostic impact of p53 and Myc protein overexpression as single or double abnormalities in overall DLBCL and GCB/ABC subtypes. Supplementary Figure S3. Heatmap for gene expression signatures of MYC/TP53 dual alterations. Supplementary Figure S4. Representative figures of flow cytometric analysis indicating G2/M phase-cell cycle arrest by NCB057643 treatment for 24 hours in cells with MYC-R or Myc overexpression with Wt-TP53 (OCI-LY19) or Mut-TP53 (GR and TMD8). Supplementary Figure S5. Heatmap for significantly up- or downregulated proteins after INCB057643 treatment (5µM, 24 hours) in OCI-LY19 cells. Supplementary Figure S6. A MDM2 inhibitor DS3032b shows cytotoxic effects selectively in high-grade B-cell lymphoma (HGBCL) with MYC/BCL2 double-hit (DH) and wild-type (Wt) TP53. Supplementary Figure S7. Combined DS3032b and INCB057643 treatment has no synergistic cytotoxicity in DLBCL cell lines with MYC aberrations and TP53 mutation (MutTP53). Supplementary Figure S8. INCB057643 treatment (1.25 µM) alone or in combination with ABT-199 (venetoclax, 6.25 mM) for 24 hours induced p21 expression in TMD8 cells, whereas had no effect on p53 (mutant) expression levels.
Supplementary Figures 1-6 from Loss of Aryl Hydrocarbon Receptor Promotes Colon Tumorigenesis in ApcS580/+; KrasG12D/+ Mice
Authors: Han Huajun , Davidson Laurie A. , Hensel Martha , Yoon Grace , Landrock Kerstin , Allred Clinton , Jayaraman Arul , Ivanov Ivan , Safe Stephen H. , Chapkin Robert S.
Published: April 2023

S1. Characterization of genotypes. S2. Loss of AhR increases non-phosphorylated β-catenin. S3. Intestinal pathology analysis from ACK and HACK mice. S4. AhR deletion promotes cell proliferation. S5. Intestinal pathology analysis from ACKG and HACKG mice. S6. Wnt signaling in Lgr5 haploinsufficient mice.
Supplementary Figure S5 from Platinum-Induced Ubiquitination of Phosphorylated H2AX by RING1A Is Mediated by Replication Protein A in Ovarian Cancer
Authors: Sriramkumar Shruthi , Matthews Timothy D. , Ghobashi Ahmed H. , Miller Samuel A. , VanderVere-Carozza Pamela S. , Pawelczak Katherine S. , Nephew Kenneth P. , Turchi John J. , O'Hagan Heather M.
Published: April 2023

RPA inhibition reduces RING1A localization to sites of cisplatin-induced DNA damage
Supplementary Fig. S5 from AXL Inhibition Induces DNA Damage and Replication Stress in Non–Small Cell Lung Cancer Cells and Promotes Sensitivity to ATR Inhibitors
Authors: Ramkumar Kavya , Stewart C. Allison , Cargill Kasey R. , Della Corte Carminia M. , Wang Qi , Shen Li , Diao Lixia , Cardnell Robert J. , Peng David H. , Rodriguez B. Leticia , Fan You-Hong , Heymach John V. , Wang Jing , Gay Carl M. , Gibbons Don L. , Byers Lauren A.
Published: April 2023

Supplementary Fig. S5: Combination of BGB324 with other DDR inhibitors.
Supplementary Table 1. from O-GlcNAc Transferase – An Auxiliary Factor or a Full-blown Oncogene?
Authors: Itkonen Harri M. , Loda Massimo , Mills Ian G.
Published: April 2023

Evaluation of OGT, OGA and O-GlcNAc levels in human cancers. Table reports the most common cancers and the studies that have evaluated the levels of OGT, OGA and O-GlcNAc, and whether or not levels were associated with disease outcome. Na=not addressed in the study in question.
Supplementary Fig. S4 from AXL Inhibition Induces DNA Damage and Replication Stress in Non–Small Cell Lung Cancer Cells and Promotes Sensitivity to ATR Inhibitors
Authors: Ramkumar Kavya , Stewart C. Allison , Cargill Kasey R. , Della Corte Carminia M. , Wang Qi , Shen Li , Diao Lixia , Cardnell Robert J. , Peng David H. , Rodriguez B. Leticia , Fan You-Hong , Heymach John V. , Wang Jing , Gay Carl M. , Gibbons Don L. , Byers Lauren A.
Published: April 2023

Supplementary Fig. S4: Sensitivity of NSCLC cell lines to ATR inhibition and AXL/ATR combination.
Supplementary Table 2 from Aberrant Claudin-6–Adhesion Signaling Promotes Endometrial Cancer Progression via Estrogen Receptor α
Authors: Kojima Manabu , Sugimoto Kotaro , Kobayashi Makoto , Ichikawa-Tomikawa Naoki , Kashiwagi Korehito , Watanabe Takafumi , Soeda Shu , Fujimori Keiya , Chiba Hideki
Published: April 2023

Supplementary Table 2 - Primers
Supplementary Table 1 from Aberrant Claudin-6–Adhesion Signaling Promotes Endometrial Cancer Progression via Estrogen Receptor α
Authors: Kojima Manabu , Sugimoto Kotaro , Kobayashi Makoto , Ichikawa-Tomikawa Naoki , Kashiwagi Korehito , Watanabe Takafumi , Soeda Shu , Fujimori Keiya , Chiba Hideki
Published: April 2023

Supplementary Table 1 - Antibodies
Supplementary Figure 1 and 2 from Colorectal Cancer-Associated Smad4 R361 Hotspot Mutations Boost Wnt/β-Catenin Signaling through Enhanced Smad4–LEF1 Binding
Authors: Lanauze Claudia B. , Sehgal Priyanka , Hayer Katharina , Torres-Diz Manuel , Pippin James A. , Grant Struan F.A. , Thomas-Tikhonenko Andrei
Published: April 2023

S1. Wnt signaling in CRC cell lines with Smad4 R361 mutations. S2. Wnt signaling in CRC cell lines with Smad4 R361 mutations.
Supplementary Figure S2 from Cross-talk between YAP and RAR-RXR Drives Expression of Stemness Genes to Promote 5-FU Resistance and Self-Renewal in Colorectal Cancer Cells
Authors: Bauzone Marjolaine , Souidi Mouloud , Dessein Anne-Frédérique , Wisztorski Maxence , Vincent Audrey , Gimeno Jean-Pascal , Monté Didier , Van Seuningen Isabelle , Gespach Christian , Huet Guillemette
Published: April 2023

Supplementary Figure S2 shows the co-occupancy by RXRalpha, RARalpha/gamma and YAP of ALDH1A3 and LGR5 proximal RAREs in control HT29 cells
Supplementary Figures 1-5 supporting the effects of MAG-EPA on prostate cancer from Omega-3 Eicosapentaenoic Acid Reduces Prostate Tumor Vascularity
Authors: Gevariya Nikunj , Lachance Gabriel , Robitaille Karine , Joly Beauparlant Charles , Beaudoin Lisanne , Fournier Éric , Fradet Yves , Droit Arnaud , Julien Pierre , Marette André , Bergeron Alain , Fradet Vincent
Published: April 2023

S1. Chronic long-chain omega-3 (LCω3) treatment blocks prostate cancer cell growth. S2. Tables of differentially expressed genes in tumors of MAG-EPA-supplemented mice. S3. Twenty men supplemented for 4-10 weeks with MAG-EPA or placebo before radical prostatectomy. S4. Stable expression of the ω3 fatty acid desaturase 1 (FAT-1) from c. elegans, which convert Ï‰6 into ω3 fatty acids, hinders prostate cancer cell growth. S5. Cytokine profiling of mouse tumors.
Supplementary Figure 4 from Metabolomics of Prostate Cancer Gleason Score in Tumor Tissue and Serum
Authors: Penney Kathryn L. , Tyekucheva Svitlana , Rosenthal Jacob , El Fandy Habiba , Carelli Ryan , Borgstein Stephanie , Zadra Giorgia , Fanelli Giuseppe Nicolò , Stefanizzi Lavinia , Giunchi Francesca , Pomerantz Mark , Peisch Samuel , Coulson Hannah , Lis Rosina , Kibel Adam S. , Fiorentino Michelangelo , Umeton Renato , Loda Massimo
Published: April 2023

Supplementary Figure 4. Heatmap of the top twenty metabolites as identified by permutation feature importance analysis of AutoML model.
Supplementary Figure 2 from Metabolomics of Prostate Cancer Gleason Score in Tumor Tissue and Serum
Authors: Penney Kathryn L. , Tyekucheva Svitlana , Rosenthal Jacob , El Fandy Habiba , Carelli Ryan , Borgstein Stephanie , Zadra Giorgia , Fanelli Giuseppe Nicolò , Stefanizzi Lavinia , Giunchi Francesca , Pomerantz Mark , Peisch Samuel , Coulson Hannah , Lis Rosina , Kibel Adam S. , Fiorentino Michelangelo , Umeton Renato , Loda Massimo
Published: April 2023

Supplementary Figure 2. Heatmap of top differential (unadjusted p<0.05) metabolites in normal prostate tissue between Gleason score 6 and Gleason score {greater than or equal to}8 tumors.
Table S1 from N-Glycosylation Patterns Correlate with Hepatocellular Carcinoma Genetic Subtypes
Authors: DelaCourt Andrew , Black Alyson , Angel Peggi , Drake Richard , Hoshida Yujin , Singal Amit , Lewin David , Taouli Bachir , Lewis Sara , Schwarz Myron , Fiel M. Isabel , Mehta Anand S.
Published: April 2023

Patient Characteristics Table
Figure S2 from N-Glycosylation Patterns Correlate with Hepatocellular Carcinoma Genetic Subtypes
Authors: DelaCourt Andrew , Black Alyson , Angel Peggi , Drake Richard , Hoshida Yujin , Singal Amit , Lewin David , Taouli Bachir , Lewis Sara , Schwarz Myron , Fiel M. Isabel , Mehta Anand S.
Published: April 2023

An overview of how HCC samples are classified into one of three subtypes based upon a variety of histological, clinical, and genetic data. Genetic data is generated through RNA-seq of the HCC samples.
Supplemental Figures 1-6 from Genomic and Transcriptomic Correlates of Thyroid Carcinoma Evolution after BRAF Inhibitor Therapy
Authors: Lee Mark , Untch Brian R. , Xu Bin , Ghossein Ronald , Han Catherine , Kuo Fengshen , Valero Cristina , Nadeem Zaineb , Patel Neal , Makarov Vladimir , Dogan Snjezana , Wong Richard J. , Sherman Eric J. , Ho Alan L. , Chan Timothy A. , Fagin James A. , Morris Luc G.T.
Published: April 2023

Supplemental Figure 1. Increased clonal heterogeneity in anaplastic metastases (ATC Met 1, 5 clones Supplemental Figure 2. Copy-number alterations for the pre-vemurafenib papillary thyroid carcinoma sample Supplemental Figure 3. Differentially expressed gene analyses comparing pre-treatment PTC sample and ATC metastases in MSK-THY1. Supplemental Figure 4. Prevalence of genetic alterations linked to BRAF inhibitor resistance and/or ATC pathogenesis in primary TCGA PTCs and metastatic/recurrent PTCs, PDTCs, and ATCs sequenced by MSK-IMPACT. Supplemental Figure 5. Histology and immunohistochemical studies for MSK-THY6. Supplemental Figure 6. Mutational landscape of tumors that underwent dedifferentiation subsequent to BRAF inhibitor targeted therapy with vemurafenib or dabrafenib.
Table S2 from Fatty Acid Oxidation Is an Adaptive Survival Pathway Induced in Prostate Tumors by HSP90 Inhibition
Authors: Nassar Zeyad D. , Mah Chui Yan , Centenera Margaret M. , Irani Swati , Sadowski Martin C. , Scott Julia S. , Nguyen Elizabeth V. , Nagarajan Shilpa R. , Moldovan Max , Lynn David J. , Daly Roger J. , Hoy Andrew J. , Butler Lisa M.
Published: April 2023

Primer sequences
Supplementary Figures and Legends 1-8 from Fatty Acid Oxidation Is an Adaptive Survival Pathway Induced in Prostate Tumors by HSP90 Inhibition
Authors: Nassar Zeyad D. , Mah Chui Yan , Centenera Margaret M. , Irani Swati , Sadowski Martin C. , Scott Julia S. , Nguyen Elizabeth V. , Nagarajan Shilpa R. , Moldovan Max , Lynn David J. , Daly Roger J. , Hoy Andrew J. , Butler Lisa M.
Published: April 2023

Figure S1. AUY922 treatment induces the expression of proteins involved in fatty acid. metabolism and increases PCa cell mitochondrial mass and cellular ROS. Figure S2. Combination treatment of AUY922 with antagonists of fatty acid oxidation (FAO) and oxidative phosphorylation reveals functional interactions. Figure S3. AUY922 and PEX act synergistically on PCa cells. Figure S4. AUY922 and PEX act synergistically on PNT1 cells. Figure S5. PEX decreased fatty acid oxidation in AUY922 treated PCa cells. Figure S6. The effect of AUY922 and PEX combination treatment on AKT, ERK and S6 signaling pathways. Figure S7. AUY922 and PEX combination treatment induces apoptosis in 22RV1 and PNT1 cells. Figure S8. AUY922 and PEX combination treatment induces apoptosis in cultured primary prostate tumors.
Supplementary Figure 4 from ADGRL4/ELTD1 Expression in Breast Cancer Cells Induces Vascular Normalization and Immune Suppression
Authors: Sheldon Helen , Bridges Esther , Silva Ildefonso , Masiero Massimo , Favara David M. , Wang Dian , Leek Russell , Snell Cameron , Roxanis Ioannis , Kreuzer Mira , Gileadi Uzi , Buffa Francesca M. , Banham Alison , Harris Adrian L.
Published: April 2023

S4. Eltd1 expressing tumour cells proliferate in the presence of endothelial cells and modifies their secretome.
Supplementary Figure 2 from ADGRL4/ELTD1 Expression in Breast Cancer Cells Induces Vascular Normalization and Immune Suppression
Authors: Sheldon Helen , Bridges Esther , Silva Ildefonso , Masiero Massimo , Favara David M. , Wang Dian , Leek Russell , Snell Cameron , Roxanis Ioannis , Kreuzer Mira , Gileadi Uzi , Buffa Francesca M. , Banham Alison , Harris Adrian L.
Published: April 2023

S2. E0771 mcoEltd1 tumours have increased vessel and M2 macrophage markers.
Supplementary Tables 1-5, Supplementary Figures 1-5 from PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E
Authors: Wang Xiaonan , Guo Qianying , Wang Hao , Yuan Xiaodong , Wang Bijun , Lobie Peter E. , Zhu Tao , Tan Sheng , Wu Zhengsheng
Published: April 2023

Table S1. Clone Primers Table S2. qPCR Primers Table S3. 3'RACE Primers Table S4. Expression of PCBP2 mRNA and protein in cancer and para-cancer tissues of breast cancer patients Table S5. Association of PCBP2 protein expression with clinicopathological parameters from breast cancer patients Fig. S1. mRNA and protein levels of PCBP2 in cancer and para-cancer normal tissues of breast cancer Fig. S2. Different 3'UTR isoforms in cancer and para-cancer normal tissues of breast cancer were verified by 3'RACE. Fig. S3 qRT-PCR analyses of the expression of PCBP2 in breast cancer cells Fig. S4. PCBP2 promotes colony formation of mammary epithelial cells in vitro Fig. S5. PCBP2 promotes the oncogenic behaviors of mammary epithelial cells via UFD1 and NT5E.
Supplementary Table S1 from Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer
Authors: Sui Yuan , Gu Ruicai , Janknecht Ralf
Published: April 2023

Correlation between JMJD1 mRNA levels in tumors.
Supplementary Figure S4 from Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer
Authors: Sui Yuan , Gu Ruicai , Janknecht Ralf
Published: April 2023

Reaction rate of JMJD1A in dependence of the oxygen concentration.
Supplementary Table 1 from Identification and Characterization of Cancer Cells That Initiate Metastases to the Brain and Other Organs
Authors: Berghoff Anna. S. , Liao Yunxiang , Karreman Matthia A. , Ilhan-Mutlu Ayseguel , Gunkel Katharina , Sprick Martin R. , Eisen Christian , Kessler Tobias , Osswald Matthias , Wünsche Susanne , Feinauer Manuel , Gril Brunhilde , Marmé Frederic , Michel Laura L. , Bago-Horvath Zuszanna , Sahm Felix , Becker Natalia , Breckwoldt Michael O. , Solecki Gergely , Gömmel Miriam , Huang Lulu , Rübmann Petra , Thome Carina M. , Ratliff Miriam , Trumpp Andreas , Steeg Patricia S. , Preusser Matthias , Wick Wolfgang , Winkler Frank
Published: April 2023

Supplementary Table 1 shows entire gene list.
Supplementary Figure S1 from Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer
Authors: Sui Yuan , Gu Ruicai , Janknecht Ralf
Published: April 2023

Relationship between HR and the three JMJD1 proteins.
Supplementary Figure 7 from Identification and Characterization of Cancer Cells That Initiate Metastases to the Brain and Other Organs
Authors: Berghoff Anna. S. , Liao Yunxiang , Karreman Matthia A. , Ilhan-Mutlu Ayseguel , Gunkel Katharina , Sprick Martin R. , Eisen Christian , Kessler Tobias , Osswald Matthias , Wünsche Susanne , Feinauer Manuel , Gril Brunhilde , Marmé Frederic , Michel Laura L. , Bago-Horvath Zuszanna , Sahm Felix , Becker Natalia , Breckwoldt Michael O. , Solecki Gergely , Gömmel Miriam , Huang Lulu , Rübmann Petra , Thome Carina M. , Ratliff Miriam , Trumpp Andreas , Steeg Patricia S. , Preusser Matthias , Wick Wolfgang , Winkler Frank
Published: April 2023

Supplementary Figure 7 shows correlation of NDRG1 expression with tumor growth in mouse and human samples.
Supplementary Figures Legends from Qa-1b Modulates Resistance to Anti–PD-1 Immune Checkpoint Blockade in Tumors with Defects in Antigen Processing
Authors: Zhang Xiao , Sabio Erich , Krishna Chirag , Ma Xiaoxiao , Wang Jingming , Jiang Hui , Havel Jonathan J. , Chan Timothy A.
Published: April 2023

Supplemental Figure Legends 1-4
Figure S4 from Qa-1b Modulates Resistance to Anti–PD-1 Immune Checkpoint Blockade in Tumors with Defects in Antigen Processing
Authors: Zhang Xiao , Sabio Erich , Krishna Chirag , Ma Xiaoxiao , Wang Jingming , Jiang Hui , Havel Jonathan J. , Chan Timothy A.
Published: April 2023

Figure S4. Representative IHC staining of CD3, CD4, and CD45 positive cells.
Supplementary Figure 1 from Identification and Characterization of Cancer Cells That Initiate Metastases to the Brain and Other Organs
Authors: Berghoff Anna. S. , Liao Yunxiang , Karreman Matthia A. , Ilhan-Mutlu Ayseguel , Gunkel Katharina , Sprick Martin R. , Eisen Christian , Kessler Tobias , Osswald Matthias , Wünsche Susanne , Feinauer Manuel , Gril Brunhilde , Marmé Frederic , Michel Laura L. , Bago-Horvath Zuszanna , Sahm Felix , Becker Natalia , Breckwoldt Michael O. , Solecki Gergely , Gömmel Miriam , Huang Lulu , Rübmann Petra , Thome Carina M. , Ratliff Miriam , Trumpp Andreas , Steeg Patricia S. , Preusser Matthias , Wick Wolfgang , Winkler Frank
Published: April 2023

Supplementary Figure 1 A-C shows loss of PKH26 over time. Supplementary Figure 1 D shows an additional example of a slow cycling cells with remaining PKH26 staining in vivo
Figure S1 from Qa-1b Modulates Resistance to Anti–PD-1 Immune Checkpoint Blockade in Tumors with Defects in Antigen Processing
Authors: Zhang Xiao , Sabio Erich , Krishna Chirag , Ma Xiaoxiao , Wang Jingming , Jiang Hui , Havel Jonathan J. , Chan Timothy A.
Published: April 2023

Fig. S1 Amplicon sequencing of the Crispr-cas9 targeting region.
Figure S1 from Deubiquitinase UCHL1 Maintains Protein Homeostasis through the PSMA7–APEH–Proteasome Axis in High-grade Serous Ovarian Carcinoma
Authors: Tangri Apoorva , Lighty Kinzie , Loganathan Jagadish , Mesmar Fahmi , Podicheti Ram , Zhang Chi , Iwanicki Marcin , Drapkin Ronny , Nakshatri Harikrishna , Mitra Sumegha
Published: April 2023

Figure S1 shows UCHL1 and p53 staining in the normal human fallopian tube and STIC.
Supplementary Table 1 from CHK2 Inhibition Provides a Strategy to Suppress Hematologic Toxicity from PARP Inhibitors
Authors: Xu Zhen , Vandenberg Cassandra J. , Lieschke Elizabeth , Di Rago Ladina , Scott Clare L. , Majewski Ian J.
Published: April 2023

Gene list for CRISPR/Cas9 DNA repair gene library. We provide a list of the genes targeted in our CRISPR/Cas9 library design. The design includes 174 DNA repair genes, 10 essential genes, Hprt1 and non-targeting controls.
Supplemental Figure 2 from Autophagy-Dependent Sensitization of Triple-Negative Breast Cancer Models to Topoisomerase II Poisons by Inhibition of the Nucleosome Remodeling Factor
Authors: Tyutyunyk-Massey Liliya , Sun Yilun , Dao Nga , Ngo Hannah , Dammalapati Mallika , Vaidyanathan Ashish , Singh Manjulata , Haqqani Syed , Haueis Joshua , Finnegan Ryan , Deng Xiaoyan , Kirberger Steve E. , Bos Paula D. , Bandyopadhyay Dipankar , Pomerantz William C.K. , Pommier Yves , Gewirtz David A. , Landry Joseph W.
Published: April 2023

Supplemental Figure 2. NURF Selectively Suppresses Toxicity to Topoisomerase 2 Poisons and Improves their DNA Damaging Effects.
Figure S1 from mDKN-01, a Novel Anti-DKK1 mAb, Enhances Innate Immune Responses in the Tumor Microenvironment
Authors: Haas Michael S. , Kagey Michael H. , Heath Heidi , Schuerpf Franziska , Rottman James B. , Newman Walter
Published: April 2023

Binding Kinetic Measurements of Human and Mouse DKN-01
Supplementary Table 1 from EGR1 Addiction in Diffuse Large B-cell Lymphoma
Authors: Kimpara Shuichi , Lu Li , Hoang Nguyet M. , Zhu Fen , Bates Paul D. , Daenthanasanmak Anusara , Zhang Shanxiang , Yang David T. , Kelm Amanda , Liu Yunxia , Li Yangguang , Rosiejka Alexander , Kondapelli Apoorv , Bebel Samantha , Chen Madelyn , Waldmann Thomas A. , Capitini Christian M. , Rui Lixin
Published: April 2023

Supplementary Table S1 including analyzed RNA-seq and ChIP-seq data
Supplementary Figure from mTOR Inhibition and T-DM1 in HER2-Positive Breast Cancer
Authors: Casadevall David , Hernández-Prat Anna , García-Alonso Sara , Arpí-Llucià Oriol , Menéndez Silvia , Qin Mengjuan , Guardia Cristina , Morancho Beatriz , Sánchez-Martín Francisco Javier , Zazo Sandra , Gavilán Elena , Sabbaghi Mohammad A. , Eroles Pilar , Cejalvo Juan Miguel , Lluch Ana , Rojo Federico , Pandiella Atanasio , Rovira Ana , Albanell Joan
Published: April 2023

Supplementary Figure from mTOR Inhibition and T-DM1 in HER2-Positive Breast Cancer
Supplementary Figure from In Vitro Insertional Mutagenesis Screen Identifies Novel Genes Driving Breast Cancer Metastasis
Authors: Miskey Csaba , Botezatu Lacramioara , Temiz Nuri A. , Gogol-Döring Andreas , Bartha Áron , Győrffy Balázs , Largaespada David A. , Ivics Zoltán , Sebe Attila
Published: April 2023

Supplementary Figure from In Vitro Insertional Mutagenesis Screen Identifies Novel Genes Driving Breast Cancer Metastasis
Supplementary Table S3 from Sox2 Is an Oncogenic Driver of Small-Cell Lung Cancer and Promotes the Classic Neuroendocrine Subtype
Authors: Voigt Ellen , Wallenburg Madeline , Wollenzien Hannah , Thompson Ethan , Kumar Kirtana , Feiner Joshua , McNally Moira , Friesen Hunter , Mukherjee Malini , Afeworki Yohannes , Kareta Michael S.
Published: April 2023

SOX2 CUT & RUN peak files
Supplementary Figure S2 from Sox2 Is an Oncogenic Driver of Small-Cell Lung Cancer and Promotes the Classic Neuroendocrine Subtype
Authors: Voigt Ellen , Wallenburg Madeline , Wollenzien Hannah , Thompson Ethan , Kumar Kirtana , Feiner Joshua , McNally Moira , Friesen Hunter , Mukherjee Malini , Afeworki Yohannes , Kareta Michael S.
Published: April 2023

Characteristics of SOX2 knockdown cell lines in Figure 2
Supplementary Figure from PARK2 Regulates eIF4B-Driven Lymphomagenesis
Authors: Kapadia Bandish B. , Roychowdhury Anirban , Kayastha Forum , Nanaji Nahid , Gartenhaus Ronald B.
Published: April 2023

Supplementary Figure from PARK2 Regulates eIF4B-Driven Lymphomagenesis
Table S1 from Hypertension Promotes the Proliferation and Migration of ccRCC Cells by Downregulation of TIMP3 in Tumor Endothelial Cells through the miR-21–5p/TGFBR2/P38/EGR1 Axis
Authors: Wang Chenguang , Xu Haibo , Liao Xinhui , Wang Weiming , Wu Wanjun , Li Wujiao , Niu Liman , Li Zhichao , Li Aolin , Sun Yangyang , Huang Weiren , Song Fei
Published: April 2023

The clinical details of ccRCC samples
Supplementary Fig S3 from Hypertension Promotes the Proliferation and Migration of ccRCC Cells by Downregulation of TIMP3 in Tumor Endothelial Cells through the miR-21–5p/TGFBR2/P38/EGR1 Axis
Authors: Wang Chenguang , Xu Haibo , Liao Xinhui , Wang Weiming , Wu Wanjun , Li Wujiao , Niu Liman , Li Zhichao , Li Aolin , Sun Yangyang , Huang Weiren , Song Fei
Published: April 2023

Supplementary Figure 3 shows the expression of TGFB1 and TIMP3 was not correlated in ccRCC，the relative luciferase activity of 3’UTR region of TIMP3 in HUVECs after TGFBR2 knockout or treatment with SB202190, and the validation of EGR1 over-expression and knockdown efficiency.
Supplementary Fig S1 from Hypertension Promotes the Proliferation and Migration of ccRCC Cells by Downregulation of TIMP3 in Tumor Endothelial Cells through the miR-21–5p/TGFBR2/P38/EGR1 Axis
Authors: Wang Chenguang , Xu Haibo , Liao Xinhui , Wang Weiming , Wu Wanjun , Li Wujiao , Niu Liman , Li Zhichao , Li Aolin , Sun Yangyang , Huang Weiren , Song Fei
Published: April 2023

Supplementary Figure 1 shows TIMP3 is a favorable prognostic marker in several tumors, and the expression distribution of TIMP3 with age, stage, and blood pressure.
Supplementary Data from cAMP-Mediated Autophagy Promotes Cell Survival via ROS-Induced Activation of PARP1: Implications for Treatment of Acute Lymphoblastic Leukemia
Authors: Richartz Nina , Pietka Wojciech , Gilljam Karin M. , Skah Seham , Skålhegg Bjørn S. , Bhagwat Sampada , Naderi Elin Hallan , Ruud Ellen , Blomhoff Heidi Kiil
Published: April 2023

Supplementary Data from cAMP-Mediated Autophagy Promotes Cell Survival via ROS-Induced Activation of PARP1: Implications for Treatment of Acute Lymphoblastic Leukemia
Supplementary Data from Glutamine Metabolism Mediates Sensitivity to Respiratory Complex II Inhibition in Acute Myeloid Leukemia
Authors: Roma Alessia , Tcheng Matthew , Ahmed Nawaz , Walker Sarah , Jayanth Preethi , Minden Mark D. , Hope Kristin , Nekkar Rao Praveen P. , Luc Jessica , Doxey Andrew C. , Reisz Julie A. , Culp-Hill Rachel , D'Alessandro Angelo , Spagnuolo Paul A.
Published: April 2023

Supplementary Data from Glutamine Metabolism Mediates Sensitivity to Respiratory Complex II Inhibition in Acute Myeloid Leukemia
Supplementary Figure from Templated Insertions Are Associated Specifically with BRCA2 Deficiency and Overall Survival in Advanced Ovarian Cancer
Authors: Moore Grace , Majumdar Rahul , Powell Simon N. , Khan Atif J. , Weinhold Nils , Yin Shen , Higginson Daniel S.
Published: April 2023

Supplementary Figure from Templated Insertions Are Associated Specifically with BRCA2 Deficiency and Overall Survival in Advanced Ovarian Cancer
Supplementary Figure from Transcriptome Profiling of ADAR1 Targets in Triple-Negative Breast Cancer Cells Reveals Mechanisms for Regulating Growth and Invasion
Authors: Baker Allison R. , Miliotis Christos , Ramírez-Moya Julia , Marc Talia , Vlachos Ioannis S. , Santisteban Pilar , Slack Frank J.
Published: April 2023

Supplementary Figure from Transcriptome Profiling of ADAR1 Targets in Triple-Negative Breast Cancer Cells Reveals Mechanisms for Regulating Growth and Invasion
Supplementary Data from Loss of VOPP1 Contributes to BET Inhibitor Acquired Resistance in Non–Small Cell Lung Cancer Cells
Authors: Sun Lin , Wu Qian , Huan Xia-Juan , Tian Chang-Qing , Wang Ying-Qing , Miao Ze-Hong
Published: April 2023

Supplementary Data from Loss of VOPP1 Contributes to BET Inhibitor Acquired Resistance in Non–Small Cell Lung Cancer Cells
Supplementary Data from Transcriptome Profiling of ADAR1 Targets in Triple-Negative Breast Cancer Cells Reveals Mechanisms for Regulating Growth and Invasion
Authors: Baker Allison R. , Miliotis Christos , Ramírez-Moya Julia , Marc Talia , Vlachos Ioannis S. , Santisteban Pilar , Slack Frank J.
Published: April 2023

Supplementary Data from Transcriptome Profiling of ADAR1 Targets in Triple-Negative Breast Cancer Cells Reveals Mechanisms for Regulating Growth and Invasion
Table S1 from DCLK1-Short Splice Variant Promotes Esophageal Squamous Cell Carcinoma Progression via the MAPK/ERK/MMP2 Pathway
Authors: Ge Yang , Fan Xiaona , Huang Xuying , Weygant Nathaniel , Xiao Zeru , Yan Rui , Liu Heshu , Liu Jian , An Guangyu , Yao Jiannan
Published: April 2023

Table S1 shows the patients cohort in TCGA database.
Supplementary Figure 5 from DCLK1-Short Splice Variant Promotes Esophageal Squamous Cell Carcinoma Progression via the MAPK/ERK/MMP2 Pathway
Authors: Ge Yang , Fan Xiaona , Huang Xuying , Weygant Nathaniel , Xiao Zeru , Yan Rui , Liu Heshu , Liu Jian , An Guangyu , Yao Jiannan
Published: April 2023

Figure S5 shows the effect of DCLK1-S re-expression on DCLK1-L mRNA level.
Figure S6 from Bone Marrow Mesenchymal Stem Cells Induce Metabolic Plasticity in Estrogen Receptor–Positive Breast Cancer
Authors: Buschhaus Johanna M. , Rajendran Shrila , Chen Siyi , Wharram Bryan L. , Bevoor Avinash S. , Cutter Alyssa C. , Humphries Brock A. , Robison Tanner H. , Farfel Alex P. , Luker Gary D.
Published: April 2023

Figure S6. Flow cytometry data for CSC stains. Cell type of interest is bolded in co-culture comparisons. A) Representative gating scheme for ALDH activity, CD24, and CD44 analyses. B-D) Flow cytometry data for MCF7 (B), T47D (C), and HCC1428 (HCC, D) cells in monoculture versus co-culture with MSCs stained for ALDH activity, CD24, and CD44. N > 10,000 cells.
Table S1 from Exosomal lincROR Promotes Docetaxel Resistance in Prostate Cancer through a β-catenin/HIF1α Positive Feedback Loop
Authors: Jiang Xingkang , Xu Yong , Liu Ranlu , Guo Shanqi
Published: April 2023

qPCR primers
Figure S4 from JMJD6 Shapes a Pro-tumor Microenvironment via ANXA1-Dependent Macrophage Polarization in Breast Cancer
Authors: Cioni Bianca , Ratti Silvia , Piva Annamaria , Tripodi Irene , Milani Matteo , Menichetti Francesca , Langella Tiziana , Botti Laura , De Cecco Loris , Chiodoni Claudia , Lecis Daniele , Colombo Mario P.
Published: April 2023

Jmjd6-mediated ANXA1 secretion promotes M2 macrophage differentiation in vitro and ex vivo. A) Mean fluorescence intensity (MFI) of M1 and M2 markers in BMDM differentiated into M0, M1 and M2.** p<0,001, *** means p<0,0001, **** p<0,00001 without conditioned medium. B) Real time PCR showing the expression M1 (CD40 and NOS2) and M2 (CD206 and ARG1) markers in BMDMs differentiated into M0, M1 and M2 macrophages without CM. Datapoints show technical replicates.** p<0,001, *** p<0,0001. C) Gating strategies for FACS analysis on ex vivo mouse samples of Figure 6D. CD45+ leukocytes were gated on live cells, excluding dead cells and debris. In CD45+ population, myeloid cells were analyzed by the expression of CD11b, Gr-1, Ly6C and F4/80 markers. Monocyte-like myleloid-derived immunosuppressive cells (M-MDSC) were identified as Ly6Chigh Gr-1int expression. Granulocyte-like myeloid-derived immunosuppressive cells (G-MDSC) were identified as Gr-1high Ly6Cint cells. M2 macrophages were identified as CD206+ cells in the F4/80 gate. G-MDSC were identified as Gr-1high Ly6Cint cells. M2 macrophages were identified as CD206+ cells in the F4/80 gate.
Figure S7 from Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling
Authors: Li Dandan , Miermont Anne M. , Sable Rushikesh , Quadri Humair S. , Mathews Griner Lesley A. , Martin Scott E. , Odzorig Taivan , De Soumita , Ferrer Marc , Powers Astin S. , Hewitt Stephen M. , Rudloff Udo
Published: April 2023

Schematic layout of the selumetinib versus 26 compounds targeting effector signaling of CNKSR1 screen; and Dose response of MK-2206 and rapamycin in the pancreas cancer cell lines.
Figure S4 from Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling
Authors: Li Dandan , Miermont Anne M. , Sable Rushikesh , Quadri Humair S. , Mathews Griner Lesley A. , Martin Scott E. , Odzorig Taivan , De Soumita , Ferrer Marc , Powers Astin S. , Hewitt Stephen M. , Rudloff Udo
Published: April 2023

CNKSR1 promotes MEK inhibition-induced AKT activation.
Figure S3 from Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling
Authors: Li Dandan , Miermont Anne M. , Sable Rushikesh , Quadri Humair S. , Mathews Griner Lesley A. , Martin Scott E. , Odzorig Taivan , De Soumita , Ferrer Marc , Powers Astin S. , Hewitt Stephen M. , Rudloff Udo
Published: April 2023

Dose response of PK-59 cells transfected with scramble siRNA and indicated candidate gene siRNAs; and CNKSR1 immunohistochemical staining in pancreas cancer tissues.
Data from Activation of the Wnt Pathway through AR79, a GSK3β Inhibitor, Promotes Prostate Cancer Growth in Soft Tissue and Bone
Authors: Jiang Yuan , Dai Jinlu , Zhang Honglai , Sottnik Joe L. , Keller Jill M. , Escott Katherine J. , Sanganee Hitesh J. , Yao Zhi , McCauley Laurie K. , Keller Evan T.
Published: April 2023

Abstract
Due to its bone anabolic activity, methods to increase Wnt activity, such as inhibitors of dickkopf-1 and sclerostin, are being clinically explored. Glycogen synthase kinase (GSK3β) inhibits Wnt signaling by inducing β-catenin degradation, and a GSK3β inhibitor, AR79, is being evaluated as an osteoanabolic agent. However, Wnt activation has the potential to promote tumor growth; therefore, the goal of this study was to determine if AR79 has an impact on the progression of prostate cancer. Prostate cancer tumors were established in subcutaneous and bone sites of mice followed by AR79 administration, and tumor growth, β-catenin activation, proliferation, and apoptosis were assessed. Additionally, prostate cancer and osteoblast cell lines were treated with AR79, and β-catenin status, proliferation (with β-catenin knockdown in some cases), and proportion of ALDH+CD133+ stem-like cells were determined. AR79 promoted prostate cancer tumor growth, decreased phospho-β-catenin, increased total and nuclear β-catenin, and increased tumor-induced bone remodeling. Additionally, AR79 treatment decreased caspase-3 and increased Ki67 expression in tumors and increased bone formation in normal mouse tibiae. Similarly, AR79 inhibited β-catenin phosphorylation, increased nuclear β-catenin accumulation in prostate cancer and osteoblast cell lines, and increased proliferation of prostate cancer cells in vitro through β-catenin. Furthermore, AR79 increased the ALDH+CD133+ cancer stem cell–like proportion of the prostate cancer cell lines. In conclusion, AR79, while being bone anabolic, promotes prostate cancer cell growth through Wnt pathway activation.

Implications: These data suggest that clinical application of pharmaceuticals that promote Wnt pathway activation should be used with caution as they may enhance tumor growth. Mol Cancer Res; 11(12); 1597–610. ©2013 AACR.
Data from MiR-335 Inhibits Small Cell Lung Cancer Bone Metastases via IGF-IR and RANKL Pathways
Authors: Gong Meng , Ma Junrong , Guillemette Ryan , Zhou Mingliang , Yang Yan , Yang Yujing , Hock Janet M. , Yu Xijie
Published: April 2023

Abstract
Small cell lung cancer (SCLC) is a rapidly progressing, incurable cancer that frequently spreads to bone. New insights are needed to identify therapeutic targets to prevent or retard SCLC metastatic progression. Human SCLC SBC-5 cells in mouse xenograft models home to skeletal and nonskeletal sites, whereas human SCLC SBC-3 cells only pervade nonskeletal sites. Because microRNAs (miRNA) often act as tumor regulators, we investigated their role in preclinical models of SCLC. miRNA expression profiling revealed selective and reduced expression of miRNA (miR)-335 and miR-29a in SBC-5 cells, compared with SBC-3 cells. In SBC-5 cells, miR-335 expression correlated with bone osteolytic lesions, whereas miR-29a expression did not. Overexpression of miR-335 in SBC-5 cells significantly reduced cell migration, invasion, proliferation, colony formation, and osteoclast induction in vitro. Importantly, in miR-335 overexpressing SBC-5 cell xenografts (n = 10), there were minimal osteolytic lesions in the majority of mice and none in three mice. Expression of RANK ligand (RANKL) and insulin-like growth factor-I receptor (IGF-IR), key mediators of bone metastases, were elevated in SBC-5 as compared with SBC-3 cells. Mechanistically, overexpression of miR-335 in SBC-5 cells reduced RANKL and IGF-IR expression. In conclusion, loss of miR-335 promoted SCLC metastatic skeletal lesions via deregulation of IGF-IR and RANKL pathways and was associated with metastatic osteolytic skeletal lesions.

Implications: These preclinical findings establish a need to pursue the role of miR-335 in human SCLC with metastatic skeletal disease. Mol Cancer Res; 12(1); 101–10. ©2013 AACR.
Data from The SmgGDS Splice Variant SmgGDS-558 Is a Key Promoter of Tumor Growth and RhoA Signaling in Breast Cancer
Authors: Hauser Andrew D. , Bergom Carmen , Schuld Nathan J. , Chen Xiuxu , Lorimer Ellen L. , Huang Jian , Mackinnon Alexander C. , Williams Carol L.
Published: April 2023

Abstract
Breast cancer malignancy is promoted by the small GTPases RhoA and RhoC. SmgGDS is a guanine nucleotide exchange factor that activates RhoA and RhoC in vitro. We previously reported that two splice variants of SmgGDS, SmgGDS-607, and SmgGDS-558, have different characteristics in binding and transport of small GTPases. To define the role of SmgGDS in breast cancer, we tested the expression of SmgGDS in breast tumors, and the role of each splice variant in proliferation, tumor growth, Rho activation, and NF-κB transcriptional activity in breast cancer cells. We show upregulated SmgGDS protein expression in breast cancer samples compared with normal breast tissue. In addition, Kaplan–Meier survival curves indicated that patients with high SmgGDS expression in their tumors had worse clinical outcomes. Knockdown of SmgGDS-558, but not SmgGDS-607, in breast cancer cells decreased proliferation, in vivo tumor growth, and RhoA activity. Furthermore, we found that SmgGDS promoted a Rho-dependent activation of the transcription factor NF-κB, which provides a potential mechanism to define how SmgGDS-mediated activation of RhoA promotes breast cancer. This study demonstrates that elevated SmgGDS expression in breast tumors correlates with poor survival, and that SmgGDS-558 plays a functional role in breast cancer malignancy. Taken together, these findings define SmgGDS-558 as a unique promoter of RhoA and NF-κB activity and a novel therapeutic target in breast cancer.

Implications: This study defines a new mechanism to regulate the activities of RhoA and NF-κB in breast cancer cells, and identifies SmgGDS-558 as a novel promoter of breast cancer malignancy. Mol Cancer Res; 12(1); 130–42. ©2013 AACR.
Data from NF-YA Underlies EZH2 Upregulation and Is Essential for Proliferation of Human Epithelial Ovarian Cancer Cells
Authors: Garipov Azat , Li Hua , Bitler Benjamin G. , Thapa Roshan J. , Balachandran Siddharth , Zhang Rugang
Published: April 2023

Abstract
Epithelial ovarian cancer (EOC) accounts for the most gynecologic malignancy–associated deaths in the United States. Enhancer of zeste homolog 2 (EZH2), which silences gene expression through generating trimethylation on lysine 27 residue of histone H3 (H3K27Me3), is often overexpressed in EOCs and has been suggested as a therapeutic target. However, the mechanism underlying EZH2 overexpression in EOCs is unknown. Here, we show that EZH2 is upregulated at the transcription level, and two CCAAT boxes in the proximal regions of the human EZH2 gene promoter are critical for its transcription in EOC cells. Indeed, NF-YA, the regulatory subunit of the CCAAT-binding transcription factor NF-Y, is expressed at higher levels in human EOCs than in primary human ovarian surface epithelial (HOSE) cells. In addition, there is a positive correlation between expression of NF-YA and EZH2 in EOCs. Notably, high NF-YA expression predicts shorter overall survival in patients with EOCs. The association of NF-YA with the promoter of the human EZH2 gene is enhanced in human EOC cells compared with primary HOSE cells. Significantly, knockdown of NF-YA downregulates EZH2, decreases H3K27Me3 levels, and suppresses the growth of human EOC cells both in vitro and in a xenograft mouse model. Notably, NF-YA knockdown induces apoptosis of EOC cells and ectopic EZH2 expression partially rescues apoptosis induced by NF-YA knockdown. Together, these data reveal that NF-Y is a key regulator of EZH2 expression and is required for EOC cell proliferation, thus representing a novel target for developing EOC therapeutics. Mol Cancer Res; 11(4); 360–9. ©2013 AACR.
Data from miRNA-302b Suppresses Human Hepatocellular Carcinoma by Targeting AKT2
Authors: Wang Lumin , Yao Jiayi , Zhang Xiaogang , Guo Bo , Le Xiaofeng , Cubberly Mark , Li Zongfang , Nan Kejun , Song Tusheng , Huang Chen
Published: April 2023

Abstract
miRNAs (miR) play a critical role in human cancers, including hepatocellular carcinoma. Although miR-302b has been suggested to function as a tumor repressor in other cancers, its role in hepatocellular carcinoma is unknown. This study investigated the expression and functional role of miR-302b in human hepatocellular carcinoma. The expression level of miR-302b is dramatically decreased in clinical hepatocellular carcinoma specimens, as compared with their respective nonneoplastic counterparts, and in hepatocellular carcinoma cell lines. Overexpression of miR-302b suppressed hepatocellular carcinoma cell proliferation and G1–S transition in vitro, whereas inhibition of miR-302b promoted hepatocellular carcinoma cell proliferation and G1–S transition. Using a luciferase reporter assay, AKT2 was determined to be a direct target of miR-302b. Subsequent investigation revealed that miR-302b expression was inversely correlated with AKT2 expression in hepatocellular carcinoma tissue samples. Importantly, silencing AKT2 recapitulated the cellular and molecular effects seen upon miR-302b overexpression, which included inhibiting hepatocellular carcinoma cell proliferation, suppressing G1 regulators (Cyclin A, Cyclin D1, CDK2) and increasing p27Kip1 phosphorylation at Ser10. Restoration of AKT2 counteracted the effects of miR-302b expression. Moreover, miR-302b was able to repress tumor growth of hepatocellular carcinoma cells in vivo.

Implications: Taken together, miR-302b inhibits HCC cell proliferation and growth in vitro and in vivo by targeting AKT2. Mol Cancer Res; 12(2); 190–202. ©2013 AACR.
Data from B56γ Tumor-Associated Mutations Provide New Mechanisms for B56γ-PP2A Tumor Suppressor Activity
Authors: Nobumori Yumiko , Shouse Geoffrey P. , Wu Yong , Lee Kyu Joon , Shen Binghui , Liu Xuan
Published: April 2023

Abstract
The hetero-trimeric PP2A serine/threonine phosphatases containing the regulatory subunit B56, and in particular B56γ, can function as tumor suppressors. In response to DNA damage, the B56γ subunit complexes with the PP2A AC core (B56γ-PP2A) and binds p53. This event promotes PP2A-mediated dephosphorylation of p53 at Thr55, which induces expression of p21, and the subsequent inhibition of cell proliferation and transformation. In addition to dephosphorylation of p53, B56γ-PP2A also inhibits cell proliferation and transformation by a second, as yet unknown, p53-independent mechanism. Here, we interrogated a panel of B56γ mutations found in human cancer samples and cell lines and showed that these mutations lost B56γ tumor-suppressive activity by two distinct mechanisms: one is by disrupting interactions with the PP2A AC core and the other with B56γ-PP2A substrates (p53 and unknown proteins). For the first mechanism, due to the absence of the C catalytic subunit in the complex, the mutants are unable to mediate dephosphorylation of any substrate and thus failed to promote both the p53-dependent and -independent tumor-suppressive functions of B56γ-PP2A. For the second mechanism, the mutants lacked specific substrate interactions and thus partially lost tumor-suppressive function, i.e., either the p53-dependent or p53-independent contingent upon which substrate binding was affected. Overall, these data provide new insight into the mechanisms of tumor suppression by B56γ.

Implications: This study further indicates the importance of B56γ-PP2A in tumorigenesis. Mol Cancer Res; 11(9); 995–1003. ©2013 AACR.
Data from Mitoxantrone Targets Human Ubiquitin-Specific Peptidase 11 (USP11) and Is a Potent Inhibitor of Pancreatic Cancer Cell Survival
Authors: Burkhart Richard A. , Peng Yu , Norris Zoë A. , Tholey Renée M. , Talbott Vanessa A. , Liang Qin , Ai Yongxing , Miller Kathy , Lal Shruti , Cozzitorto Joseph A. , Witkiewicz Agnieska K. , Yeo Charles J. , Gehrmann Matthew , Napper Andrew , Winter Jordan M. , Sawicki Janet A. , Zhuang Zhihao , Brody Jonathan R.
Published: April 2023

Abstract
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States, with a 95% five-year mortality rate. For over a decade, gemcitabine (GEM) has been the established first-line treatment for this disease despite suboptimal response rates. The development of PARP inhibitors that target the DNA damage repair (DDR) system in PDA cells has generated encouraging results. Ubiquitin-specific peptidase 11 (USP11), an enzyme that interacts with the DDR protein BRCA2, was recently discovered to play a key role in DNA double-strand break repair and may be a novel therapeutic target. A systematic high-throughput approach was used to biochemically screen 2,000 U.S. Food and Drug Administration (FDA)-approved compounds for inhibition of USP11 enzymatic activity. Six pharmacologically active small molecules that inhibit USP11 enzymatic activity were identified. An in vitro drug sensitivity assay demonstrated that one of these USP11 inhibitors, mitoxantrone, impacted PDA cell survival with an IC50 of less than 10 nM. Importantly, across six different PDA cell lines, two with defects in the Fanconi anemia/BRCA2 pathway (Hs766T and Capan-1), mitoxantrone is 40- to 20,000-fold more potent than GEM, with increased endogenous USP11 mRNA levels associated with increased sensitivity to mitoxantrone. Interestingly, USP11 silencing in PDA cells also enhanced sensitivity to GEM. These findings establish a preclinical model for the rapid discovery of FDA-approved compounds and identify USP11 as a target of mitoxantrone in PDA.

Implications: This high-throughput approach provides a strong rationale to study mitoxantrone in an early-phase clinical setting for the treatment of PDA. Mol Cancer Res; 11(8); 901–11. ©2013 AACR.