ENO1 contributes to the gemcitabine resistance of pancreatic cancer through the YAP1 signaling pathway.

Abstract

Pancreatic cancer (PC), a leading cause of cancer-related deaths, has a 5-year survival rate of approximately 10%. α-Enolase (ENO1) is a junction channel protein involved in tumor cell apoptosis and chemoresistance. However, the role of ENO1 in PC remains unclear. The expression and prognosis of ENO1 levels were determined in PC using public databases based on The Cancer Genome Atlas (TCGA) data sets. Cell viability, half maximal inhibitory concentration (IC50), autophagy, apoptosis, and autophagy markers were examined using cell counting kit-8 (CCK-8), transmission electron microscope, flow cytometry assays, and immunoblot, respectively. Using the Gene Expression Omnibus (GEO) and TCGA data sets, we found that ENO1 was significantly enriched in PC tumor tissues, and high expression levels of ENO1 were associated with an unfavorable prognosis. Whereas ENO1 silencing suppressed proliferation, autophagy, and induced cell apoptosis in PC cells, and inhibited tumor growth in vivo. Mechanistically, knockdown of ENO1 enhanced cellular cytotoxicity of gemcitabine (GEM), as well as reducing the expression of yes-associated protein 1 (YAP1), a major downstream effector of the Hippo pathway in vitro. YAP1 promoted autophagy and protected PC cells from GEM-induced apoptotic cell death. Furthermore, YAP1 overexpression attenuated the inhibition effects of ENO1 silencing. Our results suggest that ENO1 overexpression promotes cell growth and tumor progression by increasing the expression of YAP1 in PC. Further studies are required to understand the detailed mechanisms between ENO1 and YAP1 in PC.