Sitagliptin is an emerging oral hypoglycemic agent that inhibits the development of a wide variety of tumors. Current researches indicate that the abnormal activation of Yes‐associated protein (YAP) promotes the proliferation and poor prognosis of multiple tumors. However, the ability of sitagliptin to regulate YAP and its effects on gastric cancer (GC) cells remain unclear. Here, we first showed that sitagliptin inhibited the proliferation of GC cells, and this inhibition was regulated by Hippo pathway. Sitagliptin phosphorylated YAP in a large tumor suppressor homolog‐dependent manner, thereby inhibiting YAP nuclear translocation, and promoted YAP cytoplasm retention. This inhibition can be blocked by adenosine 5′‐monophosphate‐activated protein kinase (AMPK). Moreover, sitagliptin could reduce the expression of tumor‐testis antigen Melanoma‐associated antigen‐A3 through YAP. In conclusion, sitagliptin may have a potential inhibitory effect on GC by AMPK/YAP/melanoma‐associated antigen‐A3 pathway.

中文翻译：

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西他列汀通过Yes相关蛋白失活抑制黑色素瘤相关抗原A3表达，从而影响胃癌细胞的增殖。

西他列汀是一种新兴的口服降血糖药，可抑制多种肿瘤的发展。当前的研究表明，Yes相关蛋白（YAP）的异常激活会促进多发性肿瘤的增殖和不良预后。但是，西他列汀调节YAP的能力及其对胃癌（GC）细胞的影响仍不清楚。在这里，我们首先表明西他列汀可抑制GC细胞的增殖，而这种抑制作用是由Hippo途径调节的。西他列汀以较大的肿瘤抑制同源物依赖性方式磷酸化YAP，从而抑制YAP核移位，并促进YAP细胞质保留。腺苷5'-单磷酸激活蛋白激酶（AMPK）可以阻止这种抑制作用。此外，西他列汀可通过YAP降低肿瘤-睾丸抗原黑色素相关抗原A3的表达。总之，西他列汀可能通过AMPK / YAP /黑素瘤相关抗原A3途径对GC产生潜在的抑制作用。