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

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.

• Authors: Qi Wang, Pan Lu, Tao Wang, Qianqian Zheng, Yan Li, Sean X Leng, Xin Meng, Biao Wang, Jisheng Xie, Haiyan Zhang
• Journal: Cancer medicine (Cancer Med) Vol. 9 Issue 11 Pg. 3816-3828 (06 2020) ISSN: 2045-7634 [Electronic] United States
• PMID: 32227453 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Adaptor Proteins, Signal Transducing
• Antigens, Neoplasm
• Biomarkers, Tumor
• Dipeptidyl-Peptidase IV Inhibitors
• MAGEA3 protein, human
• Neoplasm Proteins
• Transcription Factors
• YAP-Signaling Proteins
• YAP1 protein, human
• Sitagliptin Phosphate

Topics

• Adaptor Proteins, Signal Transducing (antagonists & inhibitors, genetics, metabolism)
• Antigens, Neoplasm (genetics, metabolism)
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Proliferation
• Dipeptidyl-Peptidase IV Inhibitors (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Middle Aged
• Neoplasm Proteins (antagonists & inhibitors, genetics, metabolism)
• Phosphorylation
• Prognosis
• Sitagliptin Phosphate (pharmacology)
• Stomach Neoplasms (drug therapy, metabolism, pathology)
• Survival Rate
• Transcription Factors (antagonists & inhibitors, genetics, metabolism)
• Tumor Cells, Cultured
• YAP-Signaling Proteins