BREAKING INSIGHTS

3795 Highlights from Recent Cancer Literature

REVIEWS

3797 A New Switch for TGFb in CancerHsi-Wen Yeh, Szu-Shuo Lee, Chieh-Yu Chang,Yaw-Dong Lang, and Yuh-Shan Jou

3806 Cancer and the Circadian ClockAyesha A. Shafi and Karen E. Knudsen

CANCER RESEARCH HIGHLIGHTS

3815 STING (or SRC) Like an ICB: Priming the ImmuneResponse in Pancreatic CancerStanley I. Gutiontov and Ralph R. Weichselbaum

See related article, p. 3940

3818 Serine-Glycine-One-Carbon Metabolism: TheHidden Achilles Heel of MYCN-AmplifiedNeuroblastoma?Aida Rodriguez Garcia and Marie Arsenian-Henriksson

See related article, p. 3837

CONTROVERSY AND CONSENSUS

3820 Are Platelets the Primary Target of Aspirin'sRemarkable Anticancer Activity?Lenard M. Lichtenberger and K. Vinod Vijayan

METABOLISM AND CHEMICAL BIOLOGY

3824 Inhibition of Pyruvate Dehydrogenase KinaseEnhances the Antitumor Efficacy of OncolyticReovirusBarry E. Kennedy, John PatrickMurphy, Derek R. Clements,Prathyusha Konda, Namit Holay, Youra Kim,Gopal P. Pathak, Michael A. Giacomantonio,Yassine El Hiani, and Shashi Gujar

Significance: This study proposes targeted metabolicreprogramming as a valid combinatorial strategy to enhancethe translational efficacy of oncolytic virus–based cancertherapies.

3837 Metabolic Reprogramming by MYCN ConfersDependence on the Serine-Glycine-One-CarbonBiosynthetic PathwayYingfeng Xia, Bingwei Ye, Jane Ding, Yajie Yu,Ahmet Alptekin, Muthusamy Thangaraju, Puttur D. Prasad,Zhi-Chun Ding, Eun Jeong Park, Jeong-Hyeon Choi,Bei Gao, Oliver Fiehn, Chunhong Yan, Zheng Dong,Yunhong Zha, and Han-Fei Ding

Significance: This study identifies a MYCN-dependentmetabolic vulnerability and suggests a coupled relationshipbetween metabolic reprogramming and increased sensitivityto metabolic stress, which could be exploited for cancertherapy.

See related commentary p. 3818

MOLECULAR CELL BIOLOGY

3851 Dysfunction of Poly (ADP-Ribose)Glycohydrolase Induces a Synthetic Lethal Effectin Dual Specificity Phosphatase 22-DeficientLung Cancer CellsYuka Sasaki, Hiroaki Fujimori, Miyuki Hozumi,Takae Onodera, Tadashige Nozaki, Yasufumi Murakami,Kazuto Ashizawa, Kengo Inoue, Fumiaki Koizumi, andMitsuko Masutani

Significance: This study identified DUSP22 as a novelsynthetic lethal gene under the condition of PARGdysfunction and elucidated the mechanism of syntheticlethality in lung cancer cells.

3862 An ERG Enhancer–Based Reporter IdentifiesLeukemia Cells with Elevated LeukemogenicPotential Driven by ERG-USP9X Feed-ForwardRegulationNasma Aqaqe, Muhammad Yassin, Abed Alkader Yassin,Nour Ershaid, Chen Katz-Even, Adi Zipin-Roitman,Eitan Kugler, Eric R. Lechman, Olga I. Gan,Amanda Mitchell, John E. Dick, Shai Izraeli, andMichael Milyavsky

Significance: This study couples a novel experimental toolwith state-of-the-art approaches to delineate molecularmechanisms underlying stem cell-related characteristics inleukemia cells.

August 1, 2019 � Volume 79 � Number 15

Cancer Research

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3877 Genetic Ablation of the Cystine Transporter xCTin PDAC Cells Inhibits mTORC1, Growth,Survival, and Tumor Formation via Nutrient andOxidative StressesBoutaina Daher, Scott K. Parks, Jerome Durivault,Yann Cormerais, Hanane Baidarjad, Eric Tambutte,Jacques Pouyss�egur, and Milica Vu�ceti�c

Significance: The cystine/glutamate exchanger xCT isessential for amino acid and redox homeostasis and itsinhibition has potential for anticancer therapy by inducingferroptosis.

TUMOR BIOLOGY AND IMMUNOLOGY

3891 SUMO-Specific Protease 1 Is Critical for Myeloid-Derived Suppressor Cell Development andFunctionXian Huang, Yong Zuo, Xiuzhi Wang, Xuefeng Wu,Hongsheng Tan, Qiuju Fan, Baijun Dong, Wei Xue,Guo-Qiang Chen, and Jinke Cheng

Significance: These findings show that increasedSUMOylation of CD45 via loss of SENP1 suppressesCD45-mediated dephosphorylation of STAT3, whichpromotes MDSC development and function, leading totumorigenesis.

3903 Retinoblastoma Inactivation Induces aProtumoral Microenvironment via EnhancedCCL2 SecretionFengkai Li, Shunsuke Kitajima, Susumu Kohno,Akiyo Yoshida, Shoichiro Tange, Soichiro Sasaki,Nobuhiro Okada, Yuuki Nishimoto, Hayato Muranaka,Naoko Nagatani, Misa Suzuki, Sayuri Masuda,Tran C. Thai, Takumi Nishiuchi, Tomoaki Tanaka,David A. Barbie, Naofumi Mukaida, andChiaki Takahashi

Significance: These findings demonstrate the cell-nonautonomous role of the tumor suppressor retinoblastomain the tumor microenvironment, linking retinoblastoma lossto immunosuppression.

3916 CBP/p300 Drives the Differentiation ofRegulatory T Cells through Transcriptional andNon-Transcriptional MechanismsJoseph Castillo, Esther Wu, Christopher Lowe,Shrividhya Srinivasan, Ron McCord, Marie-Claire Wagle,Sangeeta Jayakar, Melissa Gonzalez Edick,Jeffrey Eastham-Anderson, Bonnie Liu,Katherine E. Hutchinson, Wendell Jones,Matthew P. Stokes, Somayeh S. Tarighat,Thomas Holcomb, Andrew Glibicky, F. Anthony Romero,Steven Magnuson, Shih-Min A. Huang, Vicki Plaks,Jennifer M. Giltnane, Mark R. Lackner, and Zineb Mounir

Significance: This study provides insights into the dynamicrole of CBP/p300 in the differentiation of Tregs, withpotential clinical implications in the alteration of theimmune landscape in follicular lymphoma.

3928 Deletion of Calcineurin Promotes aProtumorigenic Fibroblast PhenotypeAllyson Lieberman, Richard Barrett, Jaewon Kim,Kathy L. Zhang, Diana Avery, James Monslow,Hyunsoo Kim, Bang-Jin Kim, Ellen Pur�e, andSandra Ryeom

Significance: Calcineurin signaling is a key pathwayunderlying fibroblast homeostasis that could be targeted topotentially prevent fibroblast activation in distantmetastatic sites.

TRANSLATIONAL SCIENCE

3940 Inhibition of ATM Increases InterferonSignaling and Sensitizes Pancreatic Cancer toImmune Checkpoint Blockade TherapyQiang Zhang, Michael D. Green, Xueting Lang,Jenny Lazarus, Joshua D. Parsels, Shuang Wei,Leslie A. Parsels, Jiaqi Shi, Nithya Ramnath,Daniel R. Wahl, Marina Pasca di Magliano,Timothy L. Frankel, Ilona Kryczek, Yu L. Lei,Theodore S. Lawrence, Weiping Zou, andMeredith A. Morgan

Significance: This study demonstrates that ATM inhibitioninduces a T1IFN-mediated innate immune response inpancreatic cancer that is further enhanced by radiation andleads to increased sensitivity to anti–PD-L1 therapy.

See related commentary, p. 3815

CONVERGENCE AND TECHNOLOGIES

3952 Multiparametric MRI and CoregisteredHistology Identify Tumor Habitats in BreastCancer Mouse ModelsBruna V. Jardim-Perassi, Suning Huang,William Dominguez-Viqueira, Jan Poleszczuk,Mikalai M. Budzevich, Mahmoud A. Abdalah,Smitha R. Pillai, Epifanio Ruiz, Marilyn M. Bui,Debora A.P.C. Zuccari, Robert J. Gillies, andGary V. Martinez

Significance: This study demonstrates that noninvasiveimaging metrics can be used to distinguish subregionswithin heterogeneous tumors with histopathologiccorrelation.

POPULATION AND PREVENTION SCIENCE

3965 Psychologic Distress Is Associated withCancer-Specific Mortality among Patients withCervical CancerDonghao Lu, Bengt Andrae, Unnur Valdimarsdóttir,Karin Sundstr€om, Katja Fall, P€ar Spar�en, and Fang Fang

Significance: These findings support the integration ofpsychological screening and intervention in the clinicalmanagement of patients with cervical cancer, particularlyaround the time of cancer diagnosis.

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3973 Anthropometric Risk Factors for Cancers ofthe Biliary Tract in the Biliary Tract CancersPooling ProjectSarah S. Jackson, Alison L. Van Dyke, Bin Zhu,Ruth M. Pfeiffer, Jessica L. Petrick, Hans-Olov Adami,Demetrius Albanes, Gabriella Andreotti,Laura E. Beane Freeman, Amy Berrington de Gonz�alez,Julie E. Buring, Andrew T. Chan, Yu Chen, Gary E. Fraser,Neal D. Freedman, Yu-Tang Gao, Susan M. Gapstur,J. Michael Gaziano, Graham G. Giles, Eric J. Grant,Francine Grodstein, Patricia Hartge, Mazda Jenab,Cari M. Kitahara, Synnove F. Knutsen, Woon-Puay Koh,Susanna C. Larsson, I-Min Lee, Linda M. Liao, Juhua Luo,Emma E. McGee, Roger L. Milne, Kristine R. Monroe,Marian L. Neuhouser, Katie M. O’Brien, Ulrike Peters,Jenny N. Poynter, Mark P. Purdue, Kim Robien,Dale P. Sandler, Norie Sawada, Catherine Schairer,Howard D. Sesso, Tracey G. Simon, Rashmi Sinha,Rachael Z. Stolzenberg-Solomon, Shoichiro Tsugane,Renwei Wang, Elisabete Weiderpass,Stephanie J. Weinstein, Emily White, Alicja Wolk,Jian-Min Yuan, Anne Zeleniuch-Jacquotte,Xuehong Zhang, Katherine A. McGlynn,Peter T. Campbell, and Jill Koshiol

Significance: These findings identify a correlation betweenadiposity and biliary tract cancers, indicating that weightmanagement programs may help minimize the risk of thesediseases.

RESOURCE REPORT

3983 Modeling Gliomas Using Two RecombinasesToshiro Hara and Inder M. Verma

Significance: This study presents a new glioma mousemodel derived using lentiviral vectors and tworecombination systems that will expand the ability to dissectdevelopmental processes of gliomagenesis.

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ABOUT THE COVER

Mouse models for gliomas shed light on the importance of cell of origin, progression,heterogeneity, and the tumor stroma that cannot be easily studied in human cancers.GFAP-FLPo mouse strain expresses FLPo recombinase exclusively in GFAP-positive cells in thebrain, which allows restriction of the initial sources of cell of origin of gliomas with thelentiviral delivery of cancer genes. Furthermore, this glioma model enables additionalmanipulation of mouse genome mediated by Cre recombinase in any cell type at any timein vivo and, therefore, accelerates the precise understanding of cellular and molecularmechanisms in the developmental processes of this deadly disease. For details, see article byHara and Verma on page 3983.

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