HSP70-mediated mitochondrial dynamics and autophagy represent a novel vulnerability in pancreatic cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is one of the deadliest forms of cancer with limited therapy options. Overexpression of the heat shock protein 70 (HSP70) is a hallmark of cancer that is strongly associated with aggressive disease and worse clinical outcomes. However, the underlying mechanisms by which HSP70 allows tumor cells to thrive under conditions of continuous stress have not been fully described. Here, we report that PDAC has the highest expression of HSP70 relative to normal tissue across all cancers analyzed. Furthermore, HSP70 expression is associated with tumor grade and is further enhanced in metastatic PDAC. We show that genetic or therapeutic ablation of HSP70 alters mitochondrial subcellular localization, impairs mitocho

SUBMITTER: Ferretti GDS 

PROVIDER: S-EPMC11239841 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature