缺氧诱导因子、干细胞与癌症。
Hypoxia-inducible factors, stem cells, and cancer.
作者信息
Keith Brian, Simon M Celeste
机构信息
Abramson Family Cancer Research Institute, University of Pennsylvania, 453 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
出版信息
Cell. 2007 May 4;129(3):465-72. doi: 10.1016/j.cell.2007.04.019.
Abstract
Regions of severe oxygen deprivation (hypoxia) arise in tumors due to rapid cell division and aberrant blood vessel formation. The hypoxia-inducible factors (HIFs) mediate transcriptional responses to localized hypoxia in normal tissues and in cancers and can promote tumor progression by altering cellular metabolism and stimulating angiogenesis. Recently, HIFs have been shown to activate specific signaling pathways such as Notch and the expression of transcription factors such as Oct4 that control stem cell self renewal and multipotency. As many cancers are thought to develop from a small number of transformed, self-renewing, and multipotent "cancer stem cells," these results suggest new roles for HIFs in tumor progression.
摘要
由于肿瘤细胞快速分裂和异常血管生成，肿瘤内会出现严重缺氧区域（低氧）。缺氧诱导因子（HIFs）介导正常组织和癌症中对局部缺氧的转录反应，并可通过改变细胞代谢和刺激血管生成来促进肿瘤进展。最近研究表明，HIFs可激活特定信号通路，如Notch信号通路，还能激活转录因子如Oct4的表达，这些转录因子可控制干细胞自我更新和多能性。鉴于许多癌症被认为是由少数转化的、自我更新且具有多能性的“癌症干细胞”发展而来，这些结果提示了HIFs在肿瘤进展中的新作用。
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