Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Oncogene. 2010 Feb 4;29(5):625-34. doi: 10.1038/onc.2009.441. Epub 2009 Nov 30.
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 with 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 (1) clinical data associating increased HIF-1 levels with patient mortality; (2) preclinical data linking HIF-1 activity with tumor growth; (3) molecular data linking specific HIF-1 target gene products to critical aspects of cancer biology and (4) pharmacological data showing anticancer effects of HIF-1 inhibitors in mouse models of human cancer.
癌细胞适应其微环境是导致侵袭性和转移性疾病的克隆选择的重要驱动力。与正常组织相比，许多人类癌症中的氧气浓度明显降低，调节转录的主要机制是缺氧诱导因子 1（HIF-1）介导的对氧气供应减少（缺氧）的适应性反应。这篇综述总结了目前关于 HIF-1 促进癌症进展的分子机制的知识状态，重点关注：（1）与患者死亡率相关的 HIF-1 水平升高的临床数据；（2）与肿瘤生长相关的 HIF-1 活性的临床前数据；（3）将特定的 HIF-1 靶基因产物与癌症生物学的关键方面联系起来的分子数据；（4）显示 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。
