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Table of Contents

Breaking Insights

Review

Cancer Research Highlights

Genome and Epigenome

  • Pathogenic Epigenetic Consequences of Genetic Alterations in IDH-Wild-Type Diffuse Astrocytic Gliomas
    Genome and Epigenome
    Pathogenic Epigenetic Consequences of Genetic Alterations in IDH-Wild-Type Diffuse Astrocytic Gliomas
    Fumiharu Ohka, Keiko Shinjo, Shoichi Deguchi, Yusuke Matsui, Yusuke Okuno, Keisuke Katsushima, Miho Suzuki, Akira Kato, Noboru Ogiso, Akane Yamamichi, Kosuke Aoki, Hiromichi Suzuki, Shinya Sato, Nirmala Arul Rayan, Shyam Prabhakar, Jonathan Göke, Teppei Shimamura, Reo Maruyama, Satoru Takahashi, Akio Suzumura, Hiroshi Kimura, Toshihiko Wakabayashi, Hui Zong, Atsushi Natsume and Yutaka Kondo
    Cancer Res October 1 2019 79 (19) 4814-4827; DOI:10.1158/0008-5472.CAN-19-1272

    EZH2 is involved in the generation of IDH wild-type diffuse astrocytic gliomas and is a potential therapeutic target for this type of glioma.

  • Genome and Epigenome
    ERBB3 and IGF1R Signaling Are Required for Nrf2-Dependent Growth in KEAP1-Mutant Lung Cancer
    Steffan Vartanian, James Lee, Christiaan Klijn, Florian Gnad, Maria Bagniewska, Gabriele Schaefer, Donglu Zhang, Jenille Tan, Sara A. Watson, Liling Liu, Honglin Chen, Yuxin Liang, Colin Watanabe, Trinna Cuellar, David Kan, Ryan J. Hartmaier, Ted Lau, Michael R. Costa, Scott E. Martin, Mark Merchant, Benjamin Haley and David Stokoe
    Cancer Res October 1 2019 79 (19) 4828-4839; DOI:10.1158/0008-5472.CAN-18-2086

    This study identifies pathways activated by Nrf2 that are important for the proliferation and tumorigenicity of KEAP1-mutant non–small cell lung cancer.

  • Genome and Epigenome | AuthorChoice
    The Open Chromatin Landscape of Non–Small Cell Lung Carcinoma
    Zhoufeng Wang, Kailing Tu, Lin Xia, Kai Luo, Wenxin Luo, Jie Tang, Keying Lu, Xinlei Hu, Yijing He, Wenliang Qiao, Yongzhao Zhou, Jun Zhang, Feng Cao, Shuiping Dai, Panwen Tian, Ye Wang, Lunxu Liu, Guowei Che, Qinghua Zhou, Dan Xie and Weimin Li
    Cancer Res October 1 2019 79 (19) 4840-4854; DOI:10.1158/0008-5472.CAN-18-3663

    This study utilizes state of the art genomic methods to differentiate lung cancer subtypes.

Metabolism and Chemical Biology

  • Metabolism and Chemical Biology
    Dual Inhibition of GLUT1 and the ATR/CHK1 Kinase Axis Displays Synergistic Cytotoxicity in KRAS-Mutant Cancer Cells
    Johanna Erber, Joachim D. Steiner, Jörg Isensee, Leonard A. Lobbes, André Toschka, Filippo Beleggia, Anna Schmitt, Rainer W. J. Kaiser, Florian Siedek, Thorsten Persigehl, Tim Hucho and Hans C. Reinhardt
    Cancer Res October 1 2019 79 (19) 4855-4868; DOI:10.1158/0008-5472.CAN-18-3959

    Dual targeting of the DNA damage response and glucose transport synergistically induces apoptosis in KRAS-mutant cancer, suggesting this combination treatment for clinical validation in KRAS-stratified tumor patients.

Molecular Cell Biology

  • BRD4 Promotes Gastric Cancer Progression and Metastasis through Acetylation-Dependent Stabilization of Snail
    Molecular Cell Biology
    BRD4 Promotes Gastric Cancer Progression and Metastasis through Acetylation-Dependent Stabilization of Snail
    Zhong-yi Qin, Tao Wang, Siyuan Su, Li-ting Shen, Guang-xi Zhu, Qin Liu, Liang Zhang, Ke-wei Liu, Yue Zhang, Zhi-hua Zhou, Xiao-ning Zhang, Liang-zhi Wen, Yue-liang Yao, Wen-jing Sun, Yan Guo, Kai-jun Liu, Lei Liu, Xing-wei Wang, Yan-ling Wei, Jun Wang, Hua-liang Xiao, Pengda Liu, Xiu-wu Bian, Dong-feng Chen and Bin Wang
    Cancer Res October 1 2019 79 (19) 4869-4881; DOI:10.1158/0008-5472.CAN-19-0442

    These findings reveal a novel posttranscriptional regulatory function of the epigenetic reader BRD4 in cancer metastasis via stabilizing Snail, with immediate translational implication for treating metastatic malignancies with clinically available bromodomain inhibitors.

  • Molecular Cell Biology | AuthorChoice
    Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p
    Jie Xu, Qingtao Meng, Xiaobo Li, Hongbao Yang, Jin Xu, Na Gao, Hao Sun, Shenshen Wu, Giuseppe Familiari, Michela Relucenti, Haitao Zhu, Jiong Wu and Rui Chen
    Cancer Res October 1 2019 79 (19) 4882-4895; DOI:10.1158/0008-5472.CAN-18-3880

    These findings provide mechanistic insight into the role of the lncRNA MIR17HG and its miRNA members in regulating colorectal cancer carcinogenesis and progression.

  • Molecular Cell Biology
    The Cdk2–c-Myc–miR-571 Axis Regulates DNA Replication and Genomic Stability by Targeting Geminin
    Yi Zhang, Zhuqing Li, Qiang Hao, Wei Tan, Jing Sun, Jing Li, Chi-wei Chen, Zongzhu Li, Yunxiao Meng, Yuan Zhou, Zhiyong Han, Huadong Pei, Melvin L. DePamphilis and Wenge Zhu
    Cancer Res October 1 2019 79 (19) 4896-4910; DOI:10.1158/0008-5472.CAN-19-0020

    These findings identify a novel regulatory mechanism that is critical for maintaining genome integrity by regulating DNA replication and cell-cycle progression.

  • Molecular Cell Biology
    MDM2 Derived from Dedifferentiated Liposarcoma Extracellular Vesicles Induces MMP2 Production from Preadipocytes
    Lucia Casadei, Federica Calore, Danielle A. Braggio, Abeba Zewdu, Ameya A. Deshmukh, Paolo Fadda, Gonzalo Lopez, Martin Wabitsch, Chi Song, Jennifer L. Leight, Valerie P. Grignol, Dina Lev, Carlo M. Croce and Raphael E. Pollock
    Cancer Res October 1 2019 79 (19) 4911-4922; DOI:10.1158/0008-5472.CAN-19-0203

    Extracellular vesicles derived from dedifferentiated liposarcoma cells induce oncogenic properties in preadipocytes.

  • Molecular Cell Biology
    DIS3L2 Promotes Progression of Hepatocellular Carcinoma via hnRNP U-Mediated Alternative Splicing
    Songge Xing, Zhaoyong Li, Wenhao Ma, Xiaoping He, Shengqi Shen, Haoran Wei, Shi-Ting Li, Ying Shu, Linchong Sun, Xiuying Zhong, Yuhao Huangfu, Lanhong Su, Junru Feng, Xiaozhang Zhang, Ping Gao, Wei-Dong Jia and Huafeng Zhang
    Cancer Res October 1 2019 79 (19) 4923-4936; DOI:10.1158/0008-5472.CAN-19-0376

    These findings establish the role and mechanism of the 3′-5′ exoribonuclease DIS3L2 in hepatocellular carcinoma carcinogenesis.

  • Molecular Cell Biology
    Targeting the Chromosomal Passenger Complex Subunit INCENP Induces Polyploidization, Apoptosis, and Senescence in Neuroblastoma
    Ming Sun, Veronica Veschi, Sukriti Bagchi, Man Xu, Arnulfo Mendoza, Zhihui Liu and Carol J. Thiele
    Cancer Res October 1 2019 79 (19) 4937-4950; DOI:10.1158/0008-5472.CAN-19-0695

    Dysregulation of INCENP contributes to neuroblastoma tumorigenesis and targeting INCENP presents a novel strategy to disrupt the activity of chromosomal passenger complex and inhibit neuroblastoma progression.

  • Molecular Cell Biology
    LOXL2 Upregulates Phosphorylation of Ezrin to Promote Cytoskeletal Reorganization and Tumor Cell Invasion
    Xiu-Hui Zhan, Ji-Wei Jiao, Hai-Feng Zhang, Xiu-E Xu, Jian-Zhong He, Run-Liu Li, Hai-Ying Zou, Zhi-Yong Wu, Shao-Hong Wang, Jian-Yi Wu, Lian-Di Liao, Juan-Juan Wang, Yin-Wei Cheng, Kai Zhang, Gera Neufeld, Li-Yan Xu and En-Min Li
    Cancer Res October 1 2019 79 (19) 4951-4964; DOI:10.1158/0008-5472.CAN-19-0860

    LOXL2 and its spliced isoform L2Δ13 promote cytoskeletal reorganization and invasion of esophageal cancer cells by interacting with cytoplasmic actin-binding proteins such as ezrin.

  • Molecular Cell Biology
    DAXX Suppresses Tumor-Initiating Cells in Estrogen Receptor–Positive Breast Cancer Following Endocrine Therapy
    Daniel S. Peiffer, Debra Wyatt, Andrei Zlobin, Ali Piracha, Jeffrey Ng, Andrew K. Dingwall, Kathy S. Albain and Clodia Osipo
    Cancer Res October 1 2019 79 (19) 4965-4977; DOI:10.1158/0008-5472.CAN-19-1110

    Estradiol-mediated stabilization of DAXX is necessary and sufficient to repress genes associated with stemness, suggesting that the combination of endocrine therapy and DAXX-stabilizing agents may inhibit tumor recurrence in ER+ breast cancer.

  • Molecular Cell Biology | AuthorChoice
    MAP4K3/GLK Promotes Lung Cancer Metastasis by Phosphorylating and Activating IQGAP1
    Huai-Chia Chuang, Chih-Chi Chang, Chiao-Fang Teng, Chia-Hsin Hsueh, Li-Li Chiu, Pu-Ming Hsu, Ming-Ching Lee, Chung-Ping Hsu, Yi-Rong Chen, Yi-Chung Liu, Ping-Chiang Lyu and Tse-Hua Tan
    Cancer Res October 1 2019 79 (19) 4978-4993; DOI:10.1158/0008-5472.CAN-19-1402

    These findings show the critical role of the GLK–IQGAP cascade in cell migration and tumor metastasis, suggesting it as a potential biomarker and therapeutic target for lung cancer recurrence.

Tumor Biology and Immunology

  • Mutant IDH Sensitizes Gliomas to Endoplasmic Reticulum Stress and Triggers Apoptosis via miR-183-Mediated Inhibition of Semaphorin 3E
    Tumor Biology and Immunology | AuthorChoice
    Mutant IDH Sensitizes Gliomas to Endoplasmic Reticulum Stress and Triggers Apoptosis via miR-183-Mediated Inhibition of Semaphorin 3E
    Ying Zhang, Stefan Pusch, James Innes, Kastytis Sidlauskas, Matthew Ellis, Joanne Lau, Tedani El-Hassan, Natasha Aley, Francesca Launchbury, Angela Richard-Loendt, Jasper deBoer, Sheng Chen, Lei Wang, Andreas von Deimling, Ningning Li and Sebastian Brandner
    Cancer Res October 1 2019 79 (19) 4994-5007; DOI:10.1158/0008-5472.CAN-19-0054

    The pathological metabolite 2-hydroxyglutarate, generated by IDH-mutant astrocytomas, sensitizes tumor cells to ER stress and delays tumorigenesis.

  • Inactivation of Proprotein Convertases in T Cells Inhibits PD-1 Expression and Creates a Favorable Immune Microenvironment in Colorectal Cancer
    Tumor Biology and Immunology
    Inactivation of Proprotein Convertases in T Cells Inhibits PD-1 Expression and Creates a Favorable Immune Microenvironment in Colorectal Cancer
    Mercedes Tomé, Angela Pappalardo, Fabienne Soulet, José Javier López, Jone Olaizola, Yannick Leger, Marielle Dubreuil, Amandine Mouchard, Delphine Fessart, Frédéric Delom, Vincent Pitard, Dominique Bechade, Mariane Fonck, Juan Antonio Rosado, François Ghiringhelli, Julie Déchanet-Merville, Isabelle Soubeyran, Geraldine Siegfried, Serge Evrard and Abdel-Majid Khatib
    Cancer Res October 1 2019 79 (19) 5008-5021; DOI:10.1158/0008-5472.CAN-19-0086

    Protein convertase enzymatic activity is required for PD-1 expression on T cells, and inhibition of protein convertase improves T-cell targeting of microsatellite instable and stable colorectal cancer.

  • Tumor Biology and Immunology
    The Immune Contexture Associates with the Genomic Landscape in Lung Adenomatous Premalignancy
    Kostyantyn Krysan, Linh M. Tran, Brandon S. Grimes, Gregory A. Fishbein, Atsuko Seki, Brian K. Gardner, Tonya C. Walser, Ramin Salehi-Rad, Jane Yanagawa, Jay M. Lee, Sherven Sharma, Denise R. Aberle, Arum E. Spira, David A. Elashoff, William D. Wallace, Michael C. Fishbein and Steven M. Dubinett
    Cancer Res October 1 2019 79 (19) 5022-5033; DOI:10.1158/0008-5472.CAN-19-0153

    These findings identify progression-associated somatic mutations, oncogenic pathways, and association between the mutational landscape and adaptive immune responses in adenomatous premalignancy.

  • Tumor Biology and Immunology
    AMPK Alpha-1 Intrinsically Regulates the Function and Differentiation of Tumor Myeloid-Derived Suppressor Cells
    Jimena Trillo-Tinoco, Rosa A. Sierra, Eslam Mohamed, Yu Cao, Álvaro de Mingo-Pulido, Danielle L. Gilvary, Carmen M. Anadon, Tara Lee Costich, Sheng Wei, Elsa R. Flores, Brian Ruffell, José R. Conejo-Garcia and Paulo C. Rodriguez
    Cancer Res October 1 2019 79 (19) 5034-5047; DOI:10.1158/0008-5472.CAN-19-0880

    AMPKα1 regulates the immunosuppressive activity and differentiation of tumor-MDSC, suggesting AMPK inhibition as a potential therapeutic strategy to restore protective myelopoiesis in cancer.

  • Tumor Biology and Immunology
    Arming Tumor-Associated Macrophages to Reverse Epithelial Cancer Progression
    Hiromi I. Wettersten, Sara M. Weis, Paulina Pathria, Tami Von Schalscha, Toshiyuki Minami, Judith A. Varner and David A. Cheresh
    Cancer Res October 1 2019 79 (19) 5048-5059; DOI:10.1158/0008-5472.CAN-19-1246

    Therapeutic antibodies are commonly engineered to optimize engagement of NK cells as effectors. In contrast, LM609 targets αvβ3 to suppress tumor progression and enhance drug sensitivity by exploiting TAMs to trigger ADCC.

Translational Science

  • Translational Science
    Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma
    Choh Yeung, Anna E. Gibson, Sameer H. Issaq, Nobu Oshima, Joshua T. Baumgart, Leah D. Edessa, Ganesha Rai, Daniel J. Urban, Michelle S. Johnson, Gloria A. Benavides, Giuseppe L. Squadrito, Marielle E. Yohe, Haiyan Lei, Sandy Eldridge, John Hamre III, Tyrone Dowdy, Victor Ruiz-Rodado, Adrian Lita, Arnulfo Mendoza, Jack F. Shern, Mioara Larion, Lee J. Helman, Gordon M. Stott, Murali C. Krishna, Matthew D. Hall, Victor Darley-Usmar, Leonard M. Neckers and Christine M. Heske
    Cancer Res October 1 2019 79 (19) 5060-5073; DOI:10.1158/0008-5472.CAN-19-0217

    LDHA is a pharmacologically tractable EWS-FLI1 transcriptional target that regulates the glycolytic dependence of Ewing sarcoma.

  • Translational Science
    Src-Dependent DBL Family Members Drive Resistance to Vemurafenib in Human Melanoma
    Charlotte R. Feddersen, Jacob L. Schillo, Afshin Varzavand, Hayley R. Vaughn, Lexy S. Wadsworth, Andrew P. Voigt, Eliot Y. Zhu, Brooke M. Jennings, Sarah A. Mullen, Jeremy Bobera, Jesse D. Riordan, Christopher S. Stipp and Adam J. Dupuy
    Cancer Res October 1 2019 79 (19) 5074-5087; DOI:10.1158/0008-5472.CAN-19-0244

    A simple, rapid, and flexible genetic screening approach identifies genes that drive resistance to MAPK inhibitors when overexpressed in human melanoma cells.

  • Translational Science
    Tie2–FGFR1 Interaction Induces Adaptive PI3K Inhibitor Resistance by Upregulating Aurora A/PLK1/CDK1 Signaling in Glioblastoma
    Xiaolong Li, Emmanuel Martinez-Ledesma, Chen Zhang, Feng Gao, Siyuan Zheng, Jie Ding, Shaofang Wu, Nghi Nguyen, Stephan C. Clifford, Patrick Y. Wen, Keith L. Ligon, W.K. Alfred Yung and Dimpy Koul
    Cancer Res October 1 2019 79 (19) 5088-5101; DOI:10.1158/0008-5472.CAN-19-0325

    These findings provide novel insights into the mechanisms of PI3K inhibitor resistance in glioblastoma.

Convergence and Technologies

  • Convergence and Technologies
    Differential Variation Analysis Enables Detection of Tumor Heterogeneity Using Single-Cell RNA-Sequencing Data
    Emily F. Davis-Marcisak, Thomas D. Sherman, Pranay Orugunta, Genevieve L. Stein-O'Brien, Sidharth V. Puram, Evanthia T. Roussos Torres, Alexander C. Hopkins, Elizabeth M. Jaffee, Alexander V. Favorov, Bahman Afsari, Loyal A. Goff and Elana J. Fertig
    Cancer Res October 1 2019 79 (19) 5102-5112; DOI:10.1158/0008-5472.CAN-18-3882

    This study presents a robust statistical algorithm for evaluating gene expression heterogeneity within pathways or gene sets in single-cell RNA-seq data.

Population and Prevention Science

Letters to the Editor

Correction

Editor's Note

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