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Table of Contents

Breaking Insights

Reviews

Cancer Research Highlights

Genome and Epigenome

Metabolism and Chemical Biology

  • p300 Mediates Muscle Wasting in Lewis Lung Carcinoma
    Metabolism and Chemical Biology
    p300 Mediates Muscle Wasting in Lewis Lung Carcinoma
    Thomas K. Sin, James Z. Zhu, Guohua Zhang and Yi-Ping Li
    Cancer Res April 1 2019 79 (7) 1331-1342; DOI:10.1158/0008-5472.CAN-18-1653

    These findings demonstrate that tumorinduced muscle wasting in mice is abrogated by knockout, mutation of Lys39 or Asp1399, and pharmacological inhibition of p300.

  • Metabolism and Chemical Biology | AuthorChoice
    Tumor pH and Protein Concentration Contribute to the Signal of Amide Proton Transfer Magnetic Resonance Imaging
    Kevin J. Ray, Manon A. Simard, James R. Larkin, James Coates, Paul Kinchesh, Sean C. Smart, Geoff S. Higgins, Michael A. Chappell and Nicola R. Sibson
    Cancer Res April 1 2019 79 (7) 1343-1352; DOI:10.1158/0008-5472.CAN-18-2168

    These findings advance our understanding of amide proton transfer magnetic resonance imaging (APT MRI) of tumors and may improve the interpretation of APT MRI in clinical settings.

  • Metabolism and Chemical Biology
    Cytochrome c Deficiency Confers Apoptosome and Mitochondrial Dysfunction in African-American Men with Prostate Cancer
    Rahul Kumar, Tariq A. Bhat, Elise M. Walsh, Ajay K. Chaudhary, Jordan O'Malley, Johng S. Rhim, Jianmin Wang, Carl D. Morrison, Kristopher Attwood, Wiam Bshara, James L. Mohler, Neelu Yadav and Dhyan Chandra
    Cancer Res April 1 2019 79 (7) 1353-1368; DOI:10.1158/0008-5472.CAN-18-2383

    Mechanistic insights on prostate cancer health disparity among American men provide novel approaches to restore mitochondrial function, which can address therapeutic resistance and aggressiveness in African-American men with prostate cancer.

  • Metabolism and Chemical Biology
    Interplay between TRAP1 and Sirtuin-3 Modulates Mitochondrial Respiration and Oxidative Stress to Maintain Stemness of Glioma Stem Cells
    Hye-Kyung Park, Jun-Hee Hong, Young Taek Oh, Sung Soo Kim, Jinlong Yin, An-Jung Lee, Young Chan Chae, Jong Heon Kim, Sung-Hye Park, Chul-Kee Park, Myung-Jin Park, Jong Bae Park and Byoung Heon Kang
    Cancer Res April 1 2019 79 (7) 1369-1382; DOI:10.1158/0008-5472.CAN-18-2558

    Discovery and functional analysis of a TRAP1-SIRT3 complex in glioma stem cells identify potential target proteins for glioblastoma treatment.

  • Metabolism and Chemical Biology | AuthorChoice
    PAK4 Phosphorylates Fumarase and Blocks TGFβ-Induced Cell Growth Arrest in Lung Cancer Cells
    Tao Chen, Ting Wang, Wenhua Liang, Qin Zhao, Qiujing Yu, Chun-Min Ma, Lingang Zhuo, Dong Guo, Ke Zheng, Chengzhi Zhou, Shupei Wei, Wenhua Huang, Juhong Jiang, Jing Liu, Shiyue Li, Jianxing He, Yuhui Jiang and Nanshan Zhong
    Cancer Res April 1 2019 79 (7) 1383-1397; DOI:10.1158/0008-5472.CAN-18-2575

    Fumarase counteracts CSL via its metabolic activity to facilitate TGFβ-induced cell growth arrest, an effect largely blocked by PAK4-mediated phosphorylation of fumarase.

Molecular Cell Biology

  • Nutrient Stress–Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression
    Molecular Cell Biology
    Nutrient Stress–Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression
    Shi-Jiang Deng, Heng-Yu Chen, Zhu Zeng, Shichang Deng, Shuai Zhu, Zeng Ye, Chi He, Ming-Liang Liu, Kang Huang, Jian-Xin Zhong, Feng-Yu Xu, Qiang Li, Yang Liu, Chunyou Wang and Gang Zhao
    Cancer Res April 1 2019 79 (7) 1398-1412; DOI:10.1158/0008-5472.CAN-18-0419

    These findings show that lncRNA GLS-AS mediates a feedback loop of Myc and GLS, providing a potential therapeutic target for metabolic reprogramming in pancreatic cancer.

  • Loss of FOXP3 and TSC1 Accelerates Prostate Cancer Progression through Synergistic Transcriptional and Posttranslational Regulation of c-MYC
    Molecular Cell Biology
    Loss of FOXP3 and TSC1 Accelerates Prostate Cancer Progression through Synergistic Transcriptional and Posttranslational Regulation of c-MYC
    Lianpin Wu, Baozhu Yi, Shi Wei, Dapeng Rao, Youhua He, Gurudatta Naik, Sejong Bae, Xiaoguang M. Liu, Wei-Hsiung Yang, Guru Sonpavde, Runhua Liu and Lizhong Wang
    Cancer Res April 1 2019 79 (7) 1413-1425; DOI:10.1158/0008-5472.CAN-18-2049

    These results establish the principle of a synergistic action of TSC1 and FOXP3 during prostate cancer progression and provide new therapeutic targets for patients who have prostate cancer with two signaling defects.

  • Disruption of Endolysosomal RAB5/7 Efficiently Eliminates Colorectal Cancer Stem Cells
    Molecular Cell Biology | AuthorChoice
    Disruption of Endolysosomal RAB5/7 Efficiently Eliminates Colorectal Cancer Stem Cells
    Mitsunobu Takeda, Jun Koseki, Hidekazu Takahashi, Norikatsu Miyoshi, Naohiro Nishida, Junichi Nishimura, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Hirofumi Yamamoto, Hideshi Ishii, Yuichiro Doki, Masaki Mori and Naotsugu Haraguchi
    Cancer Res April 1 2019 79 (7) 1426-1437; DOI:10.1158/0008-5472.CAN-18-2192

    These findings show that endosomal/lysosomal RAB5 and RAB7, which regulate mitophagy, are essential for the survival of colon cancer stem cells.

  • Molecular Cell Biology | AuthorChoice
    4E-BP1 Is a Tumor Suppressor Protein Reactivated by mTOR Inhibition in Head and Neck Cancer
    Zhiyong Wang, Xiaodong Feng, Alfredo A. Molinolo, Daniel Martin, Lynn Vitale-Cross, Nijiro Nohata, Mizuo Ando, Amy Wahba, Panomwat Amornphimoltham, Xingyu Wu, Mara Gilardi, Michael Allevato, Victoria Wu, Dana J. Steffen, Philip Tofilon, Nahum Sonenberg, Joseph Califano, Qianming Chen, Scott M. Lippman and J. Silvio Gutkind
    Cancer Res April 1 2019 79 (7) 1438-1450; DOI:10.1158/0008-5472.CAN-18-1220

    These findings suggest that EIF4E-BP1 acts as a tumor suppressor in HNSCC and that 4E-BP1 dephosphorylation mediates the therapeutic response to mTORi, providing a mechanistic biomarker for future precision oncology trials.

  • Molecular Cell Biology | AuthorChoice
    YY1 Complex Promotes Quaking Expression via Super-Enhancer Binding during EMT of Hepatocellular Carcinoma
    Jingxia Han, Jing Meng, Shuang Chen, Xiaorui Wang, Shan Yin, Qiang Zhang, Huijuan Liu, Rong Qin, Zhongwei Li, Weilong Zhong, Chao Zhang, Heng Zhang, Yuanhao Tang, Tingting Lin, Wanfeng Gao, Xiaoyun Zhang, Lan Yang, Yanrong Liu, Hong-gang Zhou, Tao Sun and Cheng Yang
    Cancer Res April 1 2019 79 (7) 1451-1464; DOI:10.1158/0008-5472.CAN-18-2238

    These findings identify the YY1/p65/p300 complex as a regulator of QKI expression, identifying several potential therapeutic targets for the treatment of HCC.

  • Molecular Cell Biology
    STING Promotes Homeostasis via Regulation of Cell Proliferation and Chromosomal Stability
    Diana Rose E. Ranoa, Ryan C. Widau, Stephen Mallon, Akash D. Parekh, Claudia M. Nicolae, Xiaona Huang, Michael J. Bolt, Ainhoa Arina, Renate Parry, Stephen J. Kron, George-Lucian Moldovan, Nikolai N. Khodarev and Ralph R. Weichselbaum
    Cancer Res April 1 2019 79 (7) 1465-1479; DOI:10.1158/0008-5472.CAN-18-1972

    These findings provide clear mechanistic understanding of role of STING in cell-cycle regulation, which may be exploited in cancer therapy because most normal cells express STING, while many tumor cells do not.

Tumor Biology and Immunology

  • An Orally Active Galectin-3 Antagonist Inhibits Lung Adenocarcinoma Growth and Augments Response to PD-L1 Blockade
    Tumor Biology and Immunology | AuthorChoice
    An Orally Active Galectin-3 Antagonist Inhibits Lung Adenocarcinoma Growth and Augments Response to PD-L1 Blockade
    Lynda Vuong, Eleni Kouverianou, Claire M. Rooney, Brian J. McHugh, Sarah E.M. Howie, Christopher D. Gregory, Stuart J. Forbes, Neil C. Henderson, Fredrik R. Zetterberg, Ulf J. Nilsson, Hakon Leffler, Paul Ford, Anders Pedersen, Lise Gravelle, Susan Tantawi, Hans Schambye, Tariq Sethi and Alison C. MacKinnon
    Cancer Res April 1 2019 79 (7) 1480-1492; DOI:10.1158/0008-5472.CAN-18-2244

    A novel and orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and metastasis and augments response to PD-L1 blockade.

  • Anti–PD-L1 Treatment Results in Functional Remodeling of the Macrophage Compartment
    Tumor Biology and Immunology
    Anti–PD-L1 Treatment Results in Functional Remodeling of the Macrophage Compartment
    Huizhong Xiong, Stephanie Mittman, Ryan Rodriguez, Marina Moskalenko, Patricia Pacheco-Sanchez, Yagai Yang, Dorothee Nickles and Rafael Cubas
    Cancer Res April 1 2019 79 (7) 1493-1506; DOI:10.1158/0008-5472.CAN-18-3208

    This work demonstrates that increased IFNγ signaling following anti-PD-L1 treatment can remodel the macrophage compartment to enhance T-cell responses.

  • Tumor Biology and Immunology
    Cognate Nonlytic Interactions between CD8+ T Cells and Breast Cancer Cells Induce Cancer Stem Cell–like Properties
    Roland G. Stein, Stefan Ebert, Laura Schlahsa, Claus J. Scholz, Matthias Braun, Petra Hauck, Evi Horn, Camelia-Maria Monoranu, Vincent J. Thiemann, Michael P. Wustrow, Sebastian F. Häusler, Itsaso Montalbán del Barrio, Tanja N. Stüber, Matthias Wölfl, Johannes Dietl, Andreas Rosenwald, Joachim E. Diessner, Achim Wöckel and Jörg Wischhusen
    Cancer Res April 1 2019 79 (7) 1507-1519; DOI:10.1158/0008-5472.CAN-18-0387

    This study shows that ineffective immune responses not only fail to clear a malignancy, but can also activate pathways in cancer cells, which promote stemness and tumor-seeding capacity.

  • Tumor Biology and Immunology
    Tumor Suppressor miRNA-204-5p Regulates Growth, Metastasis, and Immune Microenvironment Remodeling in Breast Cancer
    Bok Sil Hong, Han Suk Ryu, Namshin Kim, Jisun Kim, Eunshin Lee, Hyunhye Moon, Kyoung Hyoun Kim, Min-Sun Jin, Nam Hoon Kwon, Sunghoon Kim, Donghyun Kim, Doo Hyun Chung, Kyeonghun Jeong, Kwangsoo Kim, Ki Yoon Kim, Han-Byoel Lee, Wonshik Han, Jihui Yun, Jong-Il Kim, Dong-Young Noh and Hyeong-Gon Moon
    Cancer Res April 1 2019 79 (7) 1520-1534; DOI:10.1158/0008-5472.CAN-18-0891

    This study demonstrates that regulation of PI3K/Akt signaling by miR-204-5p suppresses tumor metastasis and immune cell reprogramming in breast cancer.

  • Tumor Biology and Immunology | AuthorChoice
    Pomalidomide Alters Pancreatic Macrophage Populations to Generate an Immune-Responsive Environment at Precancerous and Cancerous Lesions
    Ligia I. Bastea, Geou-Yarh Liou, Veethika Pandey, Alicia K. Fleming, Christina A. von Roemeling, Heike Doeppler, Zhimin Li, Yushi Qiu, Brandy Edenfield, John A. Copland, Han W. Tun and Peter Storz
    Cancer Res April 1 2019 79 (7) 1535-1548; DOI:10.1158/0008-5472.CAN-18-1153

    These findings reveal new insights into how macrophage populations within the pancreatic cancer microenvironment can be modulated, providing the means to turn the microenvironment from immunosuppressive to immune-responsive.

  • Tumor Biology and Immunology | AuthorChoice
    Whole Genome–Derived Tiled Peptide Arrays Detect Prediagnostic Autoantibody Signatures in Non–Small-Cell Lung Cancer
    Yuanqing Yan, Nan Sun, Hong Wang, Makoto Kobayashi, Jon J. Ladd, James P. Long, Ken C. Lo, Jigar Patel, Eric Sullivan, Thomas Albert, Gary E. Goodman, Kim-Anh Do and Samir M. Hanash
    Cancer Res April 1 2019 79 (7) 1549-1557; DOI:10.1158/0008-5472.CAN-18-1536

    This study provides a modality for early diagnosis of NSCLC for precision oncology that can be applied to other cancer types.

  • Tumor Biology and Immunology
    CCL27/CCL28–CCR10 Chemokine Signaling Mediates Migration of Lymphatic Endothelial Cells
    Tara Karnezis, Rae H. Farnsworth, Nicole C. Harris, Steven P. Williams, Carol Caesar, David J. Byrne, Prad Herle, Maria L. Macheda, Ramin Shayan, You-Fang Zhang, Sezer Yazar, Simon J. Takouridis, Craig Gerard, Stephen B. Fox, Marc G. Achen and Steven A. Stacker
    Cancer Res April 1 2019 79 (7) 1558-1572; DOI:10.1158/0008-5472.CAN-18-1858

    This study shows that the remodeling of lymphatic vessels in cancer is influenced by CCL27 and CCL28 chemokines, which may serve as future targets to modulate metastatic spread.

  • Tumor Biology and Immunology
    Cervical Cancer–Instructed Stromal Fibroblasts Enhance IL23 Expression in Dendritic Cells to Support Expansion of Th17 Cells
    Barbara Walch-Rückheim, Russalina Ströder, Laura Theobald, Jennifer Pahne-Zeppenfeld, Subramanya Hegde, Yoo-Jin Kim, Rainer Maria Bohle, Ingolf Juhasz-Böss, Erich-Franz Solomayer and Sigrun Smola
    Cancer Res April 1 2019 79 (7) 1573-1586; DOI:10.1158/0008-5472.CAN-18-1913

    Cervical cancer cells differentially regulate IL23 and IL12 in DC fibroblast cocultures in an IL6/C/EBPβ/IL1β-dependent manner, thereby supporting the expansion of Th17 cells during cancer progression.

  • Tumor Biology and Immunology
    RIPK3-Induced Inflammation by I-MDSCs Promotes Intestinal Tumors
    Asha Jayakumar and Alfred L.M. Bothwell
    Cancer Res April 1 2019 79 (7) 1587-1599; DOI:10.1158/0008-5472.CAN-18-2153

    The specific role of Ripk3 in intestinal tumors and MDSC function sheds light on a key inflammatory mechanism driving tumorigenesis and allows for possible therapeutic intervention.

  • Tumor Biology and Immunology
    Nod1 Imprints Inflammatory and Carcinogenic Responses toward the Gastric Pathogen Helicobacter pylori
    Giovanni Suarez, Judith Romero-Gallo, Maria B. Piazuelo, Johanna C. Sierra, Alberto G. Delgado, M. Kay Washington, Shailja C. Shah, Keith T. Wilson and Richard M. Peek Jr
    Cancer Res April 1 2019 79 (7) 1600-1611; DOI:10.1158/0008-5472.CAN-18-2651

    These findings suggest that manipulation of NOD1 may represent a novel strategy to prevent or treat pathologic outcomes induced by H. pylori infection.

  • Tumor Biology and Immunology
    Smarcal1 and Zranb3 Protect Replication Forks from Myc-Induced DNA Replication Stress
    Matthew V. Puccetti, Clare M. Adams, Saul Kushinsky and Christine M. Eischen
    Cancer Res April 1 2019 79 (7) 1612-1623; DOI:10.1158/0008-5472.CAN-18-2705

    Smarcal1 and Zranb3 are essential, but nonredundant, for responding to DNA replication stress and stabilizing replication forks following Myc overexpression.

  • Tumor Biology and Immunology
    Local Delivery of Ox40l, Cd80, and Cd86 mRNA Kindles Global Anticancer Immunity
    Ole Audun Werner Haabeth, Timothy R. Blake, Colin J. McKinlay, Anders A. Tveita, Adrienne Sallets, Robert M. Waymouth, Paul A. Wender and Ronald Levy
    Cancer Res April 1 2019 79 (7) 1624-1634; DOI:10.1158/0008-5472.CAN-18-2867

    The mRNA-CART system is a highly effective delivery platform for delivering immunostimulatory genes into the tumor microenvironment for potential therapeutic development.

  • Tumor Biology and Immunology
    Eomes+T-betlow CD8+ T Cells Are Functionally Impaired and Are Associated with Poor Clinical Outcome in Patients with Acute Myeloid Leukemia
    Bei Jia, Chenchen Zhao, Kevin L. Rakszawski, David F. Claxton, W. Christopher Ehmann, Witold B. Rybka, Shin Mineishi, Ming Wang, Hiroko Shike, Michael G. Bayerl, Jeffrey M. Sivik, Todd D. Schell, Joseph J. Drabick, Raymond J. Hohl and Hong Zheng
    Cancer Res April 1 2019 79 (7) 1635-1645; DOI:10.1158/0008-5472.CAN-18-3107

    These findings reveal that a high frequency of Eomes+T-betlow CD8+ T cells predicts poor clinical outcome in AML and that targeting Eomes may provide a therapeutic benefit against AML.

Translational Science

  • Translational Science | AuthorChoice
    MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma In Situ
    Qianyu Guo, Vivian Z. Li, Jessica N. Nichol, Fan Huang, William Yang, Samuel E.J. Preston, Zahra Talat, Hanne Lefrère, Henry Yu, Guihua Zhang, Mark Basik, Christophe Gonçalves, Yao Zhan, Dany Plourde, Jie Su, Jose Torres, Maud Marques, Sara Al Habyan, Krikor Bijian, Frédéric Amant, Michael Witcher, Fariba Behbod, Luke McCaffrey, Moulay Alaoui-Jamali, Nadia V. Giannakopoulos, Muriel Brackstone, Lynne-Marie Postovit, Sonia V. del Rincón and Wilson H. Miller Jr
    Cancer Res April 1 2019 79 (7) 1646-1657; DOI:10.1158/0008-5472.CAN-18-1602

    These findings provide new mechanistic insight into progression of ductal carcinoma and support clinical application of MNK1 inhibitors to delay progression of indolent ductal carcinoma in situ to invasive ductal carcinoma.

  • Translational Science
    Epithelial-to-Mesenchymal Transition Is a Mechanism of ALK Inhibitor Resistance in Lung Cancer Independent of ALK Mutation Status
    Koji Fukuda, Shinji Takeuchi, Sachiko Arai, Ryohei Katayama, Shigeki Nanjo, Azusa Tanimoto, Akihiro Nishiyama, Takayuki Nakagawa, Hirokazu Taniguchi, Takeshi Suzuki, Tadaaki Yamada, Hiroshi Nishihara, Hironori Ninomiya, Yuichi Ishikawa, Satoko Baba, Kengo Takeuchi, Atsushi Horiike, Noriko Yanagitani, Makoto Nishio and Seiji Yano
    Cancer Res April 1 2019 79 (7) 1658-1670; DOI:10.1158/0008-5472.CAN-18-2052

    These findings show that dual inhibition of HDAC and ALK receptor tyrosine kinase activities provides a means to circumvent crizotinib resistance in lung cancer.

  • Translational Science
    Metastatic Tumor-in-a-Dish, a Novel Multicellular Organoid to Study Lung Colonization and Predict Therapeutic Response
    Prabhu Ramamoorthy, Sufi Mary Thomas, Gaurav Kaushik, Dharmalingam Subramaniam, Katherine M. Chastain, Animesh Dhar, Ossama Tawfik, Anup Kasi, Weijing Sun, Satish Ramalingam, Sumedha Gunewardena, Shahid Umar, Joshua M. Mammen, Subhash B. Padhye, Scott J. Weir, Roy A. Jensen, G. Sitta Sittampalam and Shrikant Anant
    Cancer Res April 1 2019 79 (7) 1681-1695; DOI:10.1158/0008-5472.CAN-18-2602

    A lung organoid that exhibits characteristics of a normal human lung was developed to study the biology of metastatic disease and therapeutic intervention.

Convergence and Technologies

Population and Prevention Science

  • Population and Prevention Science
    A miRNA Expression Signature in Breast Tumor Tissue Is Associated with Risk of Distant Metastasis
    Thomas E. Rohan, Tao Wang, Sheila Weinmann, Yihong Wang, Juan Lin, Mindy Ginsberg and Olivier Loudig
    Cancer Res April 1 2019 79 (7) 1705-1713; DOI:10.1158/0008-5472.CAN-18-2779

    A novel predictive scoring system for patients with breast cancer includes clinical variables and the expression levels of 13 miRNAs, and may help to identify those at increased risk of distant metastasis.

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