Heat shock protein 47 confers chemoresistance on pancreatic cancer cells by interacting with calreticulin and IRE1α.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most chemoresistant cancers. An understanding of the molecular mechanism by which PDAC cells have a high chemoresistant potential is important for improvement of the poor prognosis of patients with PDAC. Here we show for the first time that disruption of heat shock protein 47 (HSP47) enhances the efficacy of the therapeutic agent gemcitabine for PDAC cells and that the efficacy is suppressed by reconstituting HSP47 expression. HSP47 interacts with calreticulin (CALR) and the unfolded protein response transducer IRE1α in PDAC cells. Ablation of HSP47 promotes both the interaction of CALR with sarcoplasmic/endoplasmic reticulum Ca²⁺ -ATPase 2 and interaction of IRE1α with inositol 1,4,5-triphosphate receptor, which generates a

SUBMITTER: Yoneda A 

PROVIDER: S-EPMC8253297 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature