低氧诱导蛋白与肿瘤发生发展的研究进展

Research Advances in Hypoxia-Inducible Proteins in Cancer Progression

低氧是大多数实体肿瘤的一个重要特征。它可以导致肿瘤向恶性方向发展,使肿瘤细胞具有更强的侵袭和转移能力,并对化学治疗和放射治疗产生抵抗。在这个过程之中,以低氧诱导因子(Hypoxia-inducible factors,HIFs)为代表的一系列低氧诱导蛋白起主要调控作用,它们通过影响下游多种信号通路调节肿瘤细胞增殖、迁移、侵袭、血管生成、免疫应答、放/化疗抗性来促进或抑制肿瘤发生发展。随着对低氧诱导蛋白的深入研究,发现尽管大多数情况下低氧会促进肿瘤发生发展,但同时也存在着一小部分低氧诱导蛋白具有抑制肿瘤进展的作用。因此,对低氧诱导蛋白的研究在抗肿瘤药物开发以及肿瘤治疗方法的选择上具有重要意义。文章对HIFs以及两种新发现的低氧诱导蛋白—孕酮诱导的蜕膜蛋白(Decidual protein induced by progesterone,DEPP)和蛋白激酶A锚定蛋白(A-kinase anchor protein 4,AKAP4)在肿瘤发展和治疗中的功能加以整理总结,希望能够推动以低氧蛋白为靶点的抗肿瘤治疗在临床的应用。

Hypoxia is a significant feature in most solid cancers. It leads cancer cells to a malignant phenotype with more invasive,greater metastatic potential and resistance to chemo-or radio-therapy. Cancer hypoxic response is primarily mediated by the hypoxiainducible proteins,such as hypoxia-inducible factors（ HIFs）. Hypoxia-inducible proteins exert different effects on tumor progression and affect important cancer biological responses including cell proliferation,invasion and metastasis,angiogenesis,immune responses and resistance to chemo-or radio-therapy. However,hypoxia-inducible proteins generally have a dual effect on tumor growth. Therefore,better understanding the role of hypoxia-inducible proteins in cancer progression is very important for the development of antitumor drugs and for selecting the suitable anti-tumor therapy. To open new windows for the discovery of new anti-tumor drugs and therapeutics targeted tumor hypoxia,this review provides background knowledge on the role of HIFs,decidual protein induced by progesterone（ DEPP） and A-kinase anchor protein 4（ AKAP4） which are newly discovered in cancer progression.