Overexpression of YBX1 Promotes Pancreatic Ductal Adenocarcinoma Growth via the GSK3B/Cyclin D1/Cyclin E1 Pathway

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers due to frequently late diagnosis and futile treatment. It is a crucial necessity to determine the mechanisms of PDAC. Y-box Binding Protein 1 (YBX1), a highly conserved transcription factor, has been previously reported to play a role in various hallmarks of cancer. We show here that YBX1 is significantly overexpressed in PDAC and correlates with poor prognosis and reduced survival. In PDAC cell lines, YBX1 regulated cell-cycle progression, proliferation, and the expression of glycogen synthase kinase 3 beta (GSK3B) and cell-cycle-related proteins cyclin D1 and E1. Dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays established that YBX1 binds to the promoter of GSK3B, suggesting that YBX1 promotes pancreatic cancer cell growth through induction of GSK3B expression. These findings offer important insights into the mechanisms underlying pathologic proliferation in PDAC.