Sitagliptin affects gastric cancer cells proliferation by suppressing Melanoma-associated antigen-A3 expression through Yes-associated protein inactivation

Qi Wang, Pan Lu, Tao Wang, Qianqian Zheng, Yan Li, Sean X. Leng, Xin Meng, Biao Wang, Jisheng Xie, Haiyan Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3816-3828
Number of pages13
JournalCancer medicine
Volume9
Issue number11
DOIs
StatePublished - Jun 1 2020

Keywords

  • MAGE-A3
  • YAP
  • gastric cancer
  • sitagliptin

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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