Yap1在非小细胞肺癌发生发展及治疗中的作用

Yes相关蛋白1（yes-associated protein，Yap1）是Hippo通路的主要效应因子，在非小细胞肺癌（non-small cell lung cancer，NSCLC）中，其与高分级、淋巴结转移、病理分期晚、预后差等密切相关。Yap1促进NSCLC的增殖、侵袭及转移，促进了NSCLC肿瘤干细胞的更新及血管拟态，降低了NSCLC对化疗、放疗、表皮生长因子受体-酪氨酸激酶抑制剂（epidermal grouth factor receptor-tyrosine kinase inhibitors，EGFR-TKIs）的敏感性。同时，Yap1与抗程序性细胞死亡因子1（programmed cell death 1，PD-1）的关系提示了其在NSCLC免疫治疗中发挥一定作用。临床前研究显示，应用Yap1抑制剂可抑制NSCLC细胞增殖，减少干细胞活性，恢复药物敏感性。本文对上述问题进行综述，并探讨Yap1作为治疗靶点的重要性和必要性。 

Role of YAP1 in carcinogenesis and treatment of non-small cell lung cancer

Yes-associated protein 1 (YAP1), one of the main effectors in the Hippo signaling pathway, is significantly correlated with high tumor grade, lymph node metastasis, advanced stage, and poor prognosis in patients with non-small cell lung cancer (NSCLC). Recently, several studies have shown that YAP1 can increase proliferation, invasiveness, and migration of NSCLC cells; promote self-renewal and angiogenic mimicry of cancer stem cells; and decrease sensitivity to chemotherapy, radiotherapy, and epidermal growth factor receptor tyrosine kinase inhibitors. Moreover, the relationship between YAP1 and PD-L1 revealed the important role of YAP1 in immunotherapy against NSCLC. Further, preclinical studies reported roles of verteporfin, one drug targeting YAP1, such as inhibition of NSCLC cell proliferation, reduction in cancer stem cell activity, and restoration of treatment sensitivity. This review summarizes the above advancements, discussing the importance and necessity of target therapy against YAP1 in NSCLC.