低氧诱导因子在肿瘤干细胞介导的肿瘤发生发展中的作用

Role of hypoxia-induced factors in cancer development mediated by cancer stem cells

低氧及低氧诱导因子(HIFs)是肿瘤干细胞、转移起始细胞及其分化后代在肿瘤发生发展过程中,能够适应氧气和营养物质缺乏的主要调节因子。在白血病、胶质母细胞瘤、黑色素瘤、前列腺癌、乳腺癌、胰腺癌等肿瘤中均发现HIFs的表达上调,尤其集中表达在低氧区域。活化的HIFs可以诱导多种干性及多药耐药等基因的表达,对肿瘤及干性介导的肿瘤细胞的自我更新、能量代谢改变、侵袭转移、血管生成以及治疗抵抗均起着重要作用。因此,研究HIFs分子在干细胞介导的不同肿瘤细胞中的靶向调节作用和代谢通路的改变,将为肿瘤的靶向治疗提供新线索。

Hypoxia and hypoxia-induced factors （HIFs） are main regulators for tumor stem cells, metastasis-initiating cells and their differentiated progenies to adapt to the environment which lacks oxygen and nutrient in the process of cancer development. HIFs are up-regulated in many tumors, including leukemia, glioblastoma, melanoma, prostate cancer, breast cancer and pancreatic cancer, in where they are especially highly expressed in hypoxic regions. HIFs activation can induce expression of numerous stem cell related genes and multidrug resistance genes, which may play important roles in tumour and stem cell-mediated self-renewing, energy metabolism alternation, invasion, metastasis, angiogenesis and treatment resis-tance of neoplastic cells. Consequently, it will provide new clues for cancer therapy after investigating the role of HIFs in tar-geted regulation and metabolic pathway modulation in various stem cell-mediated tumor cells.