HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations

被引：1350

作者：

Semenza, Gregg L. ^{[1
,2
,3
,4
,5
,6
,7
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Vasc Program, Baltimore, MD USA

[2] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD USA

[6] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2013年 / 123卷 / 09期

关键词：

ENDOTHELIAL GROWTH-FACTOR; PYRUVATE-KINASE M2; PAS DOMAIN PROTEIN-1; INDUCIBLE FACTOR-1; CELLULAR ADAPTATION; GENE-TRANSCRIPTION; TUMOR ANGIOGENESIS; MAMMALIAN TARGET; CANCER CELLS; BETA-CATENIN;

D O I：

10.1172/JCI67230

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Hypoxia occurs frequently in human cancers and induces adaptive changes in cell metabolism that include a switch from oxidative phosphorylation to glycolysis, increased glycogen synthesis, and a switch from glucose to glutamine as the major substrate for fatty acid synthesis. This broad metabolic reprogramming is coordinated at the transcriptional level by HIF-1, which functions as a master regulator to balance oxygen supply and demand. HIF-1 is also activated in cancer cells by tumor suppressor (e.g., VHL) loss of function and oncogene gain of function (leading to PI3K/AKT/mTOR activity) and mediates metabolic alterations that drive cancer progression and resistance to therapy. Inhibitors of HIF-1 or metabolic enzymes may impair the metabolic flexibility of cancer cells and make them more sensitive to anticancer drugs.

引用

页码：3664 / 3671

页数：8

共 115 条

[1]

Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses [J].

Anastasiou, Dimitrios ;

Poulogiannis, George ;

Asara, John M. ;

Boxer, Matthew B. ;

Jiang, Jian-kang ;

Shen, Min ;

Bellinger, Gary ;

Sasaki, Atsuo T. ;

Locasale, Jason W. ;

Auld, Douglas S. ;

Thomas, Craig J. ;

Vander Heiden, Matthew G. ;

Cantley, Lewis C. .

SCIENCE, 2011, 334 (6060) :1278-1283

[2]

Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains [J].

Bellot, Gregory ;

Garcia-Medina, Raquel ;

Gounon, Pierre ;

Chiche, Johanna ;

Roux, Daniele ;

Pouyssegur, Jacques ;

Mazure, Nathalie M. .

MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (10) :2570-2581

[3]

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors [J].

Birsoy, Kivanc ;

Wang, Tim ;

Possemato, Richard ;

Yilmaz, Omer H. ;

Koch, Catherine E. ;

Chen, Walter W. ;

Hutchins, Amanda W. ;

Gultekin, Yetis ;

Peterson, Tim R. ;

Carette, Jan E. ;

Brummelkamp, Thijn R. ;

Clish, Clary B. ;

Sabatini, David M. .

NATURE GENETICS, 2013, 45 (01) :104-U149

[4]

A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth [J].

Bonnet, Sebastien ;

Archer, Stephen L. ;

Allalunis-Turner, Joan ;

Haromy, Alois ;

Beaulieu, Christian ;

Thompson, Richard ;

Lee, Christopher T. ;

Lopaschuk, Gary D. ;

Puttagunta, Lakshmi ;

Bonnet, Sandra ;

Harry, Gwyneth ;

Hashimoto, Kyoko ;

Porter, Christopher J. ;

Andrade, Miguel A. ;

Thebaud, Bernard ;

Michelakis, Evangelos D. .

CANCER CELL, 2007, 11 (01) :37-51

[5]

Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases [J].

Carmeliet, Peter ;

Jain, Rakesh K. .

NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (06) :417-427

[6]

REVERSION OF TRANSFORMED GLYCOLYSIS TO NORMAL BY INHIBITION OF PROTEIN-SYNTHESIS IN RAT-KIDNEY CELLS INFECTED WITH TEMPERATURE-SENSITIVE MUTANT OF ROUS-SARCOMA VIRUS [J].

CARROLL, RC ;

ASH, JF ;

VOGT, PK ;

SINGER, SJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1978, 75 (10) :5015-5019

[7]

MicroRNA-210 Controls Mitochondrial Metabolism during Hypoxia by Repressing the Iron-Sulfur Cluster Assembly Proteins ISCU1/2 [J].

Chan, Stephen Y. ;

Zhang, Ying-Yi ;

Hemann, Craig ;

Mahoney, Christopher E. ;

Zweier, Jay L. ;

Loscalzo, Joseph .

CELL METABOLISM, 2009, 10 (04) :273-284

[8]

Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1α during hypoxia -: A mechanism of O2 sensing [J].

Chandel, NS ;

McClintock, DS ;

Feliciano, CE ;

Wood, TM ;

Melendez, JA ;

Rodriguez, AM ;

Schumacker, PT .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (33) :25130-25138

[9]

Serine is a natural ligand and allosteric activator of pyruvate kinase M2 [J].

Chaneton, Barbara ;

Hillmann, Petra ;

Zheng, Liang ;

Martin, Agnes C. L. ;

Maddocks, Oliver D. K. ;

Chokkathukalam, Achuthanunni ;

Coyle, Joseph E. ;

Jankevics, Andris ;

Holding, Finn P. ;

Vousden, Karen H. ;

Frezza, Christian ;

O'Reilly, Marc ;

Gottlieb, Eyal .

NATURE, 2012, 491 (7424) :458-+

[10]

Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis [J].

Chaturvedi, Pallavi ;

Gilkes, Daniele M. ;

Wong, Carmen Chak Lui ;

Kshitiz ;

Luo, Weibo ;

Zhang, Huafeng ;

Wei, Hong ;

Takano, Naoharu ;

Schito, Luana ;

Levchenko, Andre ;

Semenza, Gregg L. .

JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (01) :189-205

← 1 2 3 4 5 6 7 8 9 10 →