Targeting cancer's metabolic co-dependencies: A landscape shaped by genotype and tissue context

被引:29
作者
Bi, Junfeng [1 ]
Wu, Sihan [1 ]
Zhang, Wenjing [1 ]
Mischel, Paul S. [1 ,2 ,3 ]
机构
[1] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA
[2] UCSD, Sch Med, Dept Pathol, La Jolla, CA 92093 USA
[3] UCSD, Sch Med, Moores Canc Ctr, La Jolla, CA 92093 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2018年 / 1870卷 / 01期
关键词
Cancer metabolism; Metabolic co-dependency; Oncogenic signaling; Tissue context; ecDNA; Heterogeneity; AMINO-ACID-METABOLISM; ATP-CITRATE LYASE; GLUTAMINE-METABOLISM; PROMOTES GLIOBLASTOMA; FUMARATE HYDRATASE; CELL-PROLIFERATION; GERMLINE MUTATIONS; IDH MUTATIONS; TCA CYCLE; MYC;
D O I
10.1016/j.bbcan.2018.05.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tumors cells reprogram their metabolism to fuel rapid growth. The ability to trace nutrient fluxes in the context of specific alterations has provided new mechanistic insight into the process of oncogenic transformation. A broad array of complementary genetic, epigenetic, transcriptional and translational mechanisms has been identified, revealing a metabolic landscape of cancer. However, cancer metabolism is not a static or uniform process, including within a single tumor. Tumor cells adapt to changing environmental conditions, profoundly shaping the enzymatic dependencies of individual cells. The underlying molecular mechanisms of adaptation, and the specific interactions between tumor genotype, oncogenic signaling, and tissue/biochemical context, remain incompletely understood. In this review, we examine dynamic aspects of how metabolic dependencies develop in cancer, shaped both by genotype and biochemical environment, and review how these interlaced processes generate targetable metabolic vulnerabilities. This article is part of a Special Issue entitled: Cancer Metabolism edited by Dr. Chi Van Dang.
引用
收藏
页码:76 / 87
页数:12
相关论文
共 132 条
[41]   The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease [J].
Giaccia, AJ ;
Simon, MC ;
Johnson, R .
GENES & DEVELOPMENT, 2004, 18 (18) :2183-2194
[42]   Amino Acid Sensing bymTORC1: Intracellular Transporters Mark the Spot [J].
Goberdhan, Deborah C. I. ;
Wilson, Clive ;
Harris, Adrian L. .
CELL METABOLISM, 2016, 23 (04) :580-589
[43]   Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures [J].
Graham, Nicholas A. ;
Minasyan, Aspram ;
Lomova, Anastasia ;
Cass, Ashley ;
Balanis, Nikolas G. ;
Friedman, Michael ;
Chan, Shawna ;
Zhao, Sophie ;
Delgado, Adrian ;
Go, James ;
Beck, Lillie ;
Hurtz, Christian ;
Ng, Carina ;
Qiao, Rong ;
ten Hoeve, Johanna ;
Palaskas, Nicolaos ;
Wu, Hong ;
Muschen, Markus ;
Multani, Asha S. ;
Port, Elisa ;
Larson, Steven M. ;
Schultz, Nikolaus ;
Braas, Daniel ;
Christofk, Heather R. ;
Mellinghoff, Ingo K. ;
Graeber, Thomas G. .
MOLECULAR SYSTEMS BIOLOGY, 2017, 13 (02)
[44]   mTORC2 Regulates Amino Acid Metabolism in Cancer by Phosphorylation of the Cystine-Glutamate Antiporter xCT [J].
Gu, Yuchao ;
Albuquerque, Claudio P. ;
Braas, Daniel ;
Zhang, Wei ;
Villa, Genaro R. ;
Bi, Junfeng ;
Ikegami, Shiro ;
Masui, Kenta ;
Gini, Beatrice ;
Yang, Huijun ;
Gahman, Timothy C. ;
Shiau, Andrew K. ;
Cloughesy, Timothy F. ;
Christofk, Heather R. ;
Zhou, Huilin ;
Guan, Kun-Liang ;
Mischel, Paul S. .
MOLECULAR CELL, 2017, 67 (01) :128-+
[45]   Defining the role of mTOR in cancer [J].
Guertin, David A. ;
Sabatini, David M. .
CANCER CELL, 2007, 12 (01) :9-22
[46]   An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR-Dependent Pathway [J].
Guo, Deliang ;
Reinitz, Felicia ;
Youssef, Mary ;
Hong, Cynthia ;
Nathanson, David ;
Akhavan, David ;
Kuga, Daisuke ;
Amzajerdi, Ali Nael ;
Soto, Horacio ;
Zhu, Shaojun ;
Babic, Ivan ;
Tanaka, Kazuhiro ;
Dang, Julie ;
Iwanami, Akio ;
Gini, Beatrice ;
DeJesus, Jason ;
Lisiero, Dominique D. ;
Huang, Tiffany T. ;
Prins, Robert M. ;
Wen, Patrick Y. ;
Robins, H. Ian ;
Prados, Michael D. ;
DeAngelis, Lisa M. ;
Mellinghoff, Ingo K. ;
Mehta, Minesh P. ;
James, C. David ;
Chakravarti, Arnab ;
Cloughesy, Timothy F. ;
Tontonoz, Peter ;
Mischel, Paul S. .
CANCER DISCOVERY, 2011, 1 (05) :442-456
[47]   EGFR Signaling Through an Akt-SREBP-1-Dependent, Rapamycin-Resistant Pathway Sensitizes Glioblastomas to Antilipogenic Therapy [J].
Guo, Deliang ;
Prins, Robert M. ;
Dang, Julie ;
Kuga, Daisuke ;
Iwanami, Akio ;
Soto, Horacio ;
Lin, Kelly Y. ;
Huang, Tiffany T. ;
Akhavan, David ;
Hock, M. Benjamin ;
Zhu, Shaojun ;
Kofman, Ava A. ;
Bensinger, Steve J. ;
Yong, William H. ;
Vinters, Harry V. ;
Horvath, Steve ;
Watson, Andrew D. ;
Kuhn, John G. ;
Robins, H. Ian ;
Mehta, Minesh P. ;
Wen, Patrick Y. ;
DeAngelis, Lisa M. ;
Prados, Michael D. ;
Mellinghoff, Ingo K. ;
Cloughesy, Timothy F. ;
Mischel, Paul S. .
SCIENCE SIGNALING, 2009, 2 (101) :ra82
[48]   Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia [J].
Haider, Syed ;
McIntyre, Alan ;
van Stiphout, Ruud G. P. M. ;
Winchester, Laura M. ;
Wigfield, Simon ;
Harris, Adrian L. ;
Buffa, Francesca M. .
GENOME BIOLOGY, 2016, 17
[49]   Metabolic Heterogeneity in Human Lung Tumors [J].
Hensley, Christopher T. ;
Faubert, Brandon ;
Yuan, Qing ;
Lev-Cohain, Naama ;
Jin, Eunsook ;
Kim, Jiyeon ;
Jiang, Lei ;
Ko, Bookyung ;
Skelton, Rachael ;
Loudat, Laurin ;
Wodzak, Michelle ;
Klimko, Claire ;
McMillan, Elizabeth ;
Butt, Yasmeen ;
Ni, Min ;
Oliver, Dwight ;
Torrealba, Jose ;
Malloy, Craig R. ;
Kernstine, Kemp ;
Lenkinski, Robert E. ;
DeBerardinis, Ralph J. .
CELL, 2016, 164 (04) :681-694