Unknown

Dataset Information

0

Reduced O-GlcNAcylation of SNAP-23 promotes cisplatin resistance by inducing exosome secretion in ovarian cancer.


ABSTRACT: Exosomes have been associated with chemoresistance in various cancers, but such a role in ovarian cancer is not yet clear. Here, using in vitro cell-based and in vivo mouse model experiments, we show that downregulation of O-GlcNAcylation, a key post-translational protein modification, promotes exosome secretion. This increases exosome-mediated efflux of cisplatin from cancer cells resulting in chemoresistance. Mechanistically, our data indicate that downregulation of O-GlcNAclation transferase (OGT) reduces O-GlcNAclation of SNAP-23. Notably, O-GlcNAcylation of SNAP-23 is vital for regulating exosome release in ovarian cancer cells. Reduced O-GlcNAclation of SNAP-23 subsequently promotes the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of SNAP-23, VAMP8, and Stx4 proteins. This enhances exosome release causing chemoresistance by increasing the efflux of intracellular cisplatin.

SUBMITTER: Qian L 

PROVIDER: S-EPMC8128872 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3668489 | biostudies-literature
| S-EPMC6276088 | biostudies-literature
| S-EPMC4949450 | biostudies-literature
| S-EPMC7296853 | biostudies-literature
| S-EPMC6397170 | biostudies-literature
| S-EPMC6379381 | biostudies-literature
| S-EPMC5240831 | biostudies-other
| S-EPMC5862571 | biostudies-literature
| S-EPMC6354392 | biostudies-literature
| S-EPMC5228053 | biostudies-literature