Inhibition of DCLK1 kinase reverses epithelial-mesenchymal transition and restores T-cell activity in pancreatic ductal adenocarcinoma.

ABSTRACT: Immunotherapy has recently become a promising cancer therapy with extensive applications of immune checkpoint inhibitors (ICIs). However, pancreatic ductal adenocarcinoma (PDAC) appears to be unresponsive to immunotherapy due to the immunosuppressive microenvironment. Recent studies showed that cancer stem cell marker DCLK1 promoted the initiation and development of PDAC. Nevertheless, the mechanism driving this process remains unclear. Here, by performing gain-of-function investigations in PDAC cell lines, we demonstrate that both DCLK1 long (DCLK1-iso1, DCLK1-AS) and short (DCLK1-iso4, DCLK1-BL) isoforms can efficiently activate EMT leading to tumor migration and invasion. Consistent with experiments in vitro, bioinformatic analysis demonstrates that DCLK1 may act as a driver of EMT acti

SUBMITTER: Ge Y 

PROVIDER: S-EPMC8739467 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature