Cancer Therapy By Targeting Hypoxia-Inducible Factor-1

被引：42
作者：
Li, Y. [2 ,3 ]
Ye, D. [1 ]
机构：
[1] Huazhong Univ Sci & Technol, Inflammat Div, Dept Pathophysiol, Tongji Med Coll, Wuhan 430030, Peoples R China
[2] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA
[3] Harvard Univ, Sch Med, Boston, MA 02215 USA
来源：
CURRENT CANCER DRUG TARGETS | 2010年 / 10卷 / 07期
基金：
中国国家自然科学基金;
关键词：
Cancer; hypoxia-inducible factor-1; angiogenesis; Warburg effects; tumor microenvironment; therapy; ENDOTHELIAL-GROWTH-FACTOR; SMALL-MOLECULE INHIBITORS; ACTIVATED PROTEIN-KINASE; RENAL-CELL CARCINOMA; FACTOR; 1-ALPHA; TUMOR-GROWTH; TRANSCRIPTIONAL ACTIVITY; FACTOR EXPRESSION; GENE-EXPRESSION; ANTITUMOR-ACTIVITY;
D O I：
10.2174/156800910793605857
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Tumors are invariably less well-oxygenated than the normal tissues from which they arise. Hypoxia-inducible factor-1 (HIF-1), a key transcriptional regulator, plays a central role in the adaptation of tumor cells to hypoxia by activating the transcription of genes, which regulate several biological processes including angiogenesis, cell proliferation, survival, glucose metabolism and migration. The expression, activity and stability of HIF-1 are not only induced in response to reduced oxygen availability but also modulated through PI-3K, MAPKs, autocrine signaling pathways, E3 ubiquitin ligases, and other regulators. The regulators and effects of HIF-1 in cancer have intensively provided us a new clue for the HIF-1 targeting anticancer therapy. This review evaluates the HIF-1 structure, the regulation mechanisms, the functions in cancer and corresponding anticancer strategies.
引用
收藏
页码：782 / 796
页数：15
相关论文
共 195 条
[1]   Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: Novel pathways and targets for anticancer therapeutics [J].
Airley, Rachel E. ;
Mobasheri, Ali .
CHEMOTHERAPY, 2007, 53 (04) :233-256
[2]  
Akakura N, 2001, CANCER RES, V61, P6548
[3]   Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell survival pathway in PC12 cells -: Protective role in apoptosis [J].
Alvarez-Tejado, M ;
Naranjo-Suárez, S ;
Jiménez, C ;
Carrera, AC ;
Landázuri, MO ;
del Peso, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (25) :22368-22374
[4]   Lack of evidence for the involvement of the phosphoinositide 3-kinase/Akt pathway in the activation of hypoxia-inducible factors by low oxygen tension [J].
Alvarez-Tejado, M ;
Alfranca, A ;
Aragonés, J ;
Vara, A ;
Landázuri, MO ;
del Peso, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (16) :13508-13517
[5]   Hypoxia-inducible factors and hypoxic cell death in tumour physiology [J].
Bacon, AL ;
Harris, AL .
ANNALS OF MEDICINE, 2004, 36 (07) :530-539
[6]  
Bae MK, 2006, ONCOL REP, V15, P1557
[7]   OS-9 interacts with hypoxia-inducible factor 1α and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1α [J].
Baek, JH ;
Mahon, PC ;
Oh, J ;
Kelly, B ;
Krishnamachary, B ;
Pearson, M ;
Chan, DA ;
Giaccia, AJ ;
Semenza, GL .
MOLECULAR CELL, 2005, 17 (04) :503-512
[8]   Spermidine/spermine N1-acetyltransferase-1 binds to hypoxia-inducible factor-1α (HIF-1α) and RACK1 and promotes ubiquitination and degradation of HIF-1α [J].
Baek, Jin H. ;
Liu, Ye V. ;
McDonald, Karin R. ;
Wesley, Jacob B. ;
Zhang, Huafeng ;
Semenza, Gregg L. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (46) :33358-33366
[9]   Growth factor-mediated induction of HDM2 positively regulates hypoxia-inducible factor 1α expression [J].
Bárdos, JI ;
Chau, NM ;
Ashcroft, M .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (07) :2905-2914
[10]  
Bartrons R, 2007, J BIOENERG BIOMEMBR, V39, P223, DOI [10.1007/s10863-007-9080-3, 10.1007/S10863-007-9080-3]
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