Department of Genetic Medicine.
Institute for Cell Engineering, and.
J Clin Invest. 2022 Jun 1;132(11). doi: 10.1172/JCI159839.
Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each of the 50 trillion cells in the adult human body. Cancer cells co-opt this homeostatic system to drive cancer progression. HIFs activate the transcription of thousands of genes that mediate angiogenesis, cancer stem cell specification, cell motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose and lipid metabolism, immune evasion, invasion, and metastasis. In this Review, the mechanisms and consequences of HIF activation in cancer cells are presented. The current status and future prospects of small-molecule HIF inhibitors for use as cancer therapeutics are discussed.
缺氧诱导因子（HIFs）是氧平衡的主要调节剂，可匹配成人身体中 50 万亿个细胞的每个细胞的 O2 供应和需求。癌细胞利用这种体内平衡系统来推动癌症进展。HIF 激活数千个基因的转录，这些基因介导血管生成、癌症干细胞特化、细胞运动性、上皮-间充质转化、细胞外基质重塑、葡萄糖和脂质代谢、免疫逃逸、侵袭和转移。在这篇综述中，介绍了 HIF 在癌细胞中激活的机制和后果。讨论了作为癌症治疗剂使用的小分子 HIF 抑制剂的现状和未来前景。
