Reprogramming of fatty acid metabolism in cancer

被引:982
作者
Koundouros, Nikos [1 ]
Poulogiannis, George [1 ,2 ]
机构
[1] Inst Canc Res, Div Canc Biol, Signalling & Canc Metab Team, 237 Fulham Rd, London SW3 6JB, England
[2] Imperial Coll London, Dept Surg & Canc, Div Computat & Syst Med, London SW7 2AZ, England
关键词
DE-NOVO LIPOGENESIS; STEAROYL-COA-DESATURASE; ATP-CITRATE LYASE; PHOSPHATIDYLINOSITOL TRANSFER PROTEIN; GLYCOGEN-SYNTHASE KINASE-3; PENTOSE-PHOSPHATE PATHWAY; LYSOPHOSPHATIDIC ACID; PROSTAGLANDIN E-2; LIPID-METABOLISM; CELL-GROWTH;
D O I
10.1038/s41416-019-0650-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A common feature of cancer cells is their ability to rewire their metabolism to sustain the production of ATP and macromolecules needed for cell growth, division and survival. In particular, the importance of altered fatty acid metabolism in cancer has received renewed interest as, aside their principal role as structural components of the membrane matrix, they are important secondary messengers, and can also serve as fuel sources for energy production. In this review, we will examine the mechanisms through which cancer cells rewire their fatty acid metabolism with a focus on four main areas of research. (1) The role of de novo synthesis and exogenous uptake in the cellular pool of fatty acids. (2) The mechanisms through which molecular heterogeneity and oncogenic signal transduction pathways, such as PI3K-AKT-mTOR signalling, regulate fatty acid metabolism. (3) The role of fatty acids as essential mediators of cancer progression and metastasis, through remodelling of the tumour microenvironment. (4) Therapeutic strategies and considerations for successfully targeting fatty acid metabolism in cancer. Further research focusing on the complex interplay between oncogenic signalling and dysregulated fatty acid metabolism holds great promise to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.
引用
收藏
页码:4 / 22
页数:19
相关论文
共 229 条
[91]   Lysophosphatidic acid induces cell migration through the selective activation of Akt1 [J].
Kim, Eun Kyoung ;
Yun, Sung Ji ;
Do, Kee Hun ;
Kim, Min Sung ;
Cho, Mong ;
Suh, Dong-Soo ;
Kim, Chi Dae ;
Kim, Jae Ho ;
Birnbaum, Morris J. ;
Bae, Sun Sik .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2008, 40 (04) :445-452
[92]   Regulatory role of glycogen synthase kinase 3 for transcriptional activity of ADD1/SREBP1c [J].
Kim, KH ;
Song, MJ ;
Yoo, EJ ;
Choe, SS ;
Park, SD ;
Kim, JB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (50) :51999-52006
[93]   Metabolic control of epigenetics in cancer [J].
Kinnaird, Adam ;
Zhao, Steven ;
Wellen, Kathryn E. ;
Michelakis, Evangelos D. .
NATURE REVIEWS CANCER, 2016, 16 (11) :694-707
[94]   Asparagine bioavailability governs metastasis in a model of breast cancer [J].
Knott, Simon R. V. ;
Wagenblast, Elvin ;
Khan, Showkhin ;
Kim, Sun Y. ;
Soto, Mar ;
Wagner, Michel ;
Turgeon, Marc-Olivier ;
Fish, Lisa ;
Erard, Nicolas ;
Gable, Annika L. ;
Maceli, Ashley R. ;
Dickopf, Steffen ;
Papachristou, Evangelia K. ;
D'Santos, Clive S. ;
Carey, Lisa A. ;
Wilkinson, John E. ;
Harrell, J. Chuck ;
Perou, Charles M. ;
Goodarzi, Hani ;
Poulogiannis, George ;
Hannon, Gregory J. .
NATURE, 2018, 554 (7692) :378-+
[95]   Hierarchical clustering of activated proteins in the PI3K and MAPK pathways in ER-positive, HER2-negative breast cancer with potential therapeutic consequences [J].
Kruger, Dinja T. ;
Beelen, Karin J. ;
Opdam, Mark ;
Sanders, Joyce ;
van der Noort, Vincent ;
Boven, Epie ;
Linn, Sabine C. .
BRITISH JOURNAL OF CANCER, 2018, 119 (07) :832-839
[96]   FATTY-ACID SYNTHESIS - A POTENTIAL SELECTIVE TARGET FOR ANTINEOPLASTIC THERAPY [J].
KUHAJDA, FP ;
JENNER, K ;
WOOD, FD ;
HENNIGAR, RA ;
JACOBS, LB ;
DICK, JD ;
PASTERNACK, GR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (14) :6379-6383
[97]   Role of acyl-CoA synthetase ACSL4 in arachidonic acid metabolism [J].
Kuwata, Hiroshi ;
Hara, Shuntaro .
PROSTAGLANDINS & OTHER LIPID MEDIATORS, 2019, 144
[98]   Inhibition of long-chain acyl-CoA synthetase 4 facilitates production of 5, 11-dihydroxyeicosatetraenoic acid via the cyclooxygenase-2 pathway [J].
Kuwata, Hiroshi ;
Hara, Shuntaro .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2015, 465 (03) :528-533
[99]   The Role of Cholesterol in Cancer [J].
Kuzu, Omer F. ;
Noory, Mohammad A. ;
Robertson, Gavin P. .
CANCER RESEARCH, 2016, 76 (08) :2063-2070
[100]   Adipocyte-induced CD36 expression drives ovarian cancer progression and metastasis [J].
Ladanyi, Andras ;
Mukherjee, Abir ;
Kenny, Hilary A. ;
Johnson, Alyssa ;
Mitra, Anirban K. ;
Sundaresan, Sinju ;
Nieman, Kristin M. ;
Pascual, Gloria ;
Aznar Benitah, Salvador ;
Montag, Anthony ;
Yamada, S. Diane ;
Abumrad, Nada A. ;
Lengyel, Ernst .
ONCOGENE, 2018, 37 (17) :2285-2301