Yes-associated protein enhances proliferation and attenuates sensitivity to cisplatin in human gastric cancer cells.

Background Yes-associated protein (YAP) is upregulated in many cancer types, and its overexpression is involved in tumor cell proliferation, metastasis and resistance to chemotherapy. In the present study, we aimed to investigate the potential role of YAP in the development and progression of gastric cancer. Methods YAP levels were analyzed in human gastric cancer and adjacent normal tissues by Western blotting and immunohistochemistry. Potential roles of YAP in regulating gastric cancer cell proliferation and sensitivity to cisplatin were examined by genetic manipulation in vitro . The molecular signaling was determined to understand the mechanisms of observed YAP effects. Results YAP level was higher in gastric cancer tissues as compared to paired normal tissues. Knockdown of YAP attenuated gastric cancer cell proliferation and enhanced sensitivity to cisplatin in vitro while YAP overexpression possessed the opposite effects. YAP regulated Epidermal growth factor receptor (EGFR) expression and its downstream AKT and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway in gastric cancer cells. Conclusion YAP enhances gastric cancer cell proliferation and attenuates sensitivity to cisplatin potentially through targeting the EGFR signaling, indicating that YAP/EGFR signaling axis may serve as a potential target for treatment of gastric cancer. [ABSTRACT FROM AUTHOR]