HIPPO信号通路与T2DM和恶性肿瘤相关性的研究进展

Relationship Between HIPPO Signaling Pathway and Type 2 Diabetes Mellitus and Malignant Tumor

2型糖尿病(T2DM)与多种恶性肿瘤的风险升高及不良预后具有相关性,但针对两种疾病关联机制的研究较少。HIPPO信号通路在细胞的增殖、生长、凋亡及肿瘤的发生中起着关键作用。本文通过总结多项研究,提出T2DM可调节HIPPO信号通路并进一步影响恶性肿瘤发生及发展的观点。HIPPO信号通路可受糖代谢调节,在T2DM患者及小鼠模型的不同组织中观察到,HIPPO信号通路的核心成分Yes-相关蛋白(YAP)表达增加及活性提高,且YAP的表达与T2DM的一些临床表现具有相关性。在恶性肿瘤中,YAP被认为是可促进肿瘤的发生及发展的癌基因。在一些恶性肿瘤中,合并T2DM的患者相比未合并T2DM的患者,其YAP的表达增加,并且具有一些恶性进展的表现。因此,HIPPO信号通路极可能是T2DM影响恶性肿瘤的中间信号通路。

Type 2 diabetes mellitus(T2DM)is associated with increased risk and poor prognosis of various malignant tumors.However,there are few studies on the mechanism of association between them.The HIPPO signaling pathway plays a key role in cell proliferation,growth,apoptosis and tumorigenesis.In this paper,several studies are reviewed,and it is suggested that T2DM can affect the occurrence and development of malignant tumors by regulating the HIPPO signaling pathway.The HIPPO signaling pathway can be regulated by glucose metabolism.An increase of YAP,a core component of the HIPPO signaling pathway,is observed in different tissues of patients with T2DM and mouse models.In addition,the expression of YAP is related to some clinical manifestations of T2DM.In malignant tumors,YAP is considered to be an oncogene that can promote tumor occurrence and development.In some malignant tumors,compared with those without T2DM,the expression of YAP in tumor tissues of patients with T2DM is increased,and some manifestations of malignant progress appear.Therefore,the HIPPO signaling pathway is probably an intermediate signaling pathway of T2DM affecting malignant tumors.