目前全球仍面临着癌症的疾病负担,YAP (Yes-associated protein)作为Hippo信号通路的中央调节器,对组织生长修复、器官大小和干细胞的重编程起着重要的调控作用。本文综述了YAP的最新研究进展、在各个系统中YAP的表达情况以及部分致癌机制,为癌症治疗新靶点的研究提供相关理论依据。
Currently, the world is still facing the disease burden of cancer. As the central regulator of Hippo signaling pathway, YAP (YES-associated protein) plays an important role in regulating tissue growth, repair, organ size and stem cell reprogramming. This paper reviews the latest research progress of YAP, the expression of YAP in various systems and some carcinogenic mechanisms, providing relevant theoretical basis for the study of new targets for cancer treatment.
2Affiliated Hospital of Qinghai University, Xining Qinghai
Received: Apr. 27th, 2022; accepted: May 21st, 2022; published: May 31st, 2022
ABSTRACT
Currently, the world is still facing the disease burden of cancer. As the central regulator of Hippo signaling pathway, YAP (YES-associated protein) plays an important role in regulating tissue growth, repair, organ size and stem cell reprogramming. This paper reviews the latest research progress of YAP, the expression of YAP in various systems and some carcinogenic mechanisms, providing relevant theoretical basis for the study of new targets for cancer treatment.
Hippo通路与参与发育和再生的多个信号通路产生交集 [35],如Wnt通路 [36] [37],在胃肠道组织中发挥重要作用:① YAP可以抑制Wnt信号通路中的GSK-3β,阻断GSK-3β对β-catenin的磷酸化降解,激活Wnt信号通路,使β-catenin由胞质入核;在细胞核内,转录共激活因子YAP促进入核的转录激活因子β-catenin与TCF/LEF结合,诱导C-myc的表达,促进细胞的增殖、分化;② YAP可以与Wnt通路上游位于胞膜的Frizzled受体结合,抑制Wnt通路的激活;在细胞质内,YAP可以与APC、Axin、β-catenin形成的复合物结合,共同被GSK-3β磷酸化降解,抑制Wnt通路的激活。除了Wnt信号通路之外,Hippo通路与转化生长因子β (TGFβ)信号也有广泛的相互作用,还可以调节Notch, Sonic Hedgehog (Shh)和有丝分裂生长因子通路。Hippo通路和其他信号通路之间的相互作用可能有助于Hippo通路的细胞自主和非细胞自主功能。
5.3. YAP在调节性T细胞介导的抗肿瘤免疫抑制中起重要作用
调节性T细胞(Regulatory T cells, Treg)具有免疫抑制功能,对肿瘤细胞具有抑制、杀灭作用,从而维持着体内的免疫稳态,若其功能受到抑制,则会加大肿瘤细胞逃脱免疫监视的可能。Treg细胞的功能通过FoxP3呈现,FoxP3是一种转录因子,与Treg细胞功能的表达密切相关,YAP可以诱导Treg细胞的分化,影响Treg细胞的免疫抑制功能,进而影响FoxP3的表达,促进肿瘤细胞的增殖。因此,有研究者认为YAP是Treg增强途径的增强因子,具有作为抗癌免疫治疗靶点的重要潜力 [38]。
徐梦蝶,王丰梅,郑小影. 泛癌治疗新靶点——YAPA New Therapeutic Target of Pan-Cancer—YAP[J]. 临床医学进展, 2022, 12(05): 4758-4764. https://doi.org/10.12677/ACM.2022.125690
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