Hippo通路在感染及肿瘤免疫中的相关作用研究进展

Research advances on the roles of Hippo pathway in inflammation and tumor immunity

Hippo通路是通过4个主要激酶Hippo(Hpo)、Salvador(Sav)、Warts(Wts)和Mob肿瘤抑制因子(Mats)调控Yes相关蛋白(Yap/Yki)的活性,调控细胞增殖、凋亡和分化,进而控制器官体积大小的信号通路。近年研究发现,Hippo通路在不同的局部微环境以及各信号分子相互影响下显示出多样性,且在炎症和免疫应答中具有重要的调控作用,如在果蝇体内的抗微生物作用,在哺乳动物中的抗感染作用,以及参与肿瘤免疫反应等。Hippo信号通路的关键蛋白Yap活化状态有助于肿瘤细胞免于免疫清除,并可上调趋化因子CXCL5的分泌,促进免疫抑制细胞髓源性抑制细胞(MDSCs)的募集而引发肿瘤免疫逃逸,同时还能在mRNA和蛋白水平调控程序死亡配体1(PD-L1)的转录和翻译等。全面了解Hippo通路,对于研究肿瘤潜在的分子治疗靶点具有重要意义。

Hippo pathway, regulating the activity of related Yes protein (Yap/Yki) by four major kinases: Hipdo (Hpo), Salvador (Sav), Warts (Wts) and Mob tumor suppressor (Mats), regulates the cell proliferation, apoptosis and differentiation, and further controls the organ size. In recent years, it has been found that Hippo pathway is diverse in different local micro-environments and under the interaction of various signal molecules, and plays an important role in inflammation and immune response: antimicrobial effect in Drosophila sp., anti-infection effect in mammals, and participation in tumor immune response, etc. The activation state of the key protein, Yap, of the Hippo signal pathway helps to protect the tumor cells from immune clearance, up-regulates the secretion of the chemokine CXCL5, and promotes the immune escape of the tumor immune from the recruitment of the myeloidderived suppressor cells (MDSCs) of the immunosuppressive cells;transcription and translation of death ligand 1 (PD-L1) by Yap in the regulation of mRNA and protein levels. A comprehensive understanding of Hippo pathway is of great significance for the study of potential molecular therapeutic targets for tumors.