Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics.
Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics.
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DOI：
10.1038/onc.2009.441
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发表时间：
2010-02-04
期刊：
影响因子：
8
通讯作者：
Semenza, G. L.
中科院分区：
文献类型：
--
作者：
Semenza, G. L.
癌细胞对其微环境的适应是导致侵袭性和转移性疾病的克隆选择中的重要驱动力。与正常组织相比，许多人类癌症中的O2浓度显著降低，并且介导对减少的O2可用性（缺氧）的适应性反应的主要机制是通过缺氧诱导因子1（HIF-1）调节转录。本文综述了HIF-1促进肿瘤进展的分子机制的研究现状，重点是（i）HIF-1水平升高与患者死亡率相关的临床数据;（ii）HIF-1活性与肿瘤生长相关的临床前数据;（iii）HIF-1靶基因产物与肿瘤生物学关键方面相关的分子数据;和（iv）证明HIF-1抑制剂在人类癌症小鼠模型中的抗癌作用的药理学数据。
Adaptation of cancer cells to their microenvironment is an important driving force in the clonal selection that leads to invasive and metastatic disease. O2 concentrations are markedly reduced in many human cancers compared to normal tissue and a major mechanism mediating adaptive responses to reduced O2 availability (hypoxia) is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). This review summarizes the current state of knowledge regarding the molecular mechanisms by which HIF-1 contributes to cancer progression, focusing on (i) clinical data associating increased HIF-1 levels with patient mortality; (ii) preclinical data linking HIF-1 activity with tumor growth; (iii) molecular data linking specific HIF-1 target gene products to critical aspects of cancer biology; and (iv) pharmacological data demonstrating anti-cancer effects of HIF-1 inhibitors in mouse models of human cancer.
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