GRP78-mediated antioxidant response and ABC transporter activity confers chemoresistance to pancreatic cancer cells.

ABSTRACT: Chemoresistance is a major therapeutic challenge that plays a role in the poor statistical outcomes in pancreatic cancer. Unfolded protein response (UPR) is one of the homeostasis mechanisms in cancer cells that have been correlated with chemoresistance in a number of cancers including pancreatic cancer. In this study, we show that modulating glucose regulatory protein 78 (GRP78), the master regulator of the UPR, can have a profound effect on multiple pathways that mediate chemoresistance. Our study showed for the first time that silencing GRP78 can diminish efflux activity of ATP-binding cassette (ABC) transporters, and it can decrease the antioxidant response resulting in an accumulation of reactive oxygen species (ROS). We also show that these effects can be mediated by the activity of

SUBMITTER: Dauer P 

PROVIDER: S-EPMC6120253 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature