Journal
CANCER MEDICINE
Volume 9, Issue 11, Pages 3816-3828Publisher
WILEY
DOI: 10.1002/cam4.3024
Keywords
gastric cancer; MAGE-A3; sitagliptin; YAP
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Funding
- Science and Technology Research Project of Shenyang [18013056]
- National Natural Science Foundation of China [81560362, 81572831]
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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.
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