GAIP interacting protein C-terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways.

Published

Journal Article

GAIP interacting protein C terminus (GIPC) is known to play an important role in a variety of physiological and disease states. In the present study, we have identified a novel role for GIPC as a master regulator of autophagy and the exocytotic pathways in cancer. We show that depletion of GIPC-induced autophagy in pancreatic cancer cells, as evident from the upregulation of the autophagy marker LC3II. We further report that GIPC regulates cellular trafficking pathways by modulating the secretion, biogenesis, and molecular composition of exosomes. We also identified the involvement of GIPC on metabolic stress pathways regulating autophagy and microvesicular shedding, and observed that GIPC status determines the loading of cellular cargo in the exosome. Furthermore, we have shown the overexpression of the drug resistance gene ABCG2 in exosomes from GIPC-depleted pancreatic cancer cells. We also demonstrated that depletion of GIPC from cancer cells sensitized them to gemcitabine treatment, an avenue that can be explored as a potential therapeutic strategy to overcome drug resistance in cancer.

Full Text

Duke Authors

Cited Authors

  • Bhattacharya, S; Pal, K; Sharma, AK; Dutta, SK; Lau, JS; Yan, IK; Wang, E; Elkhanany, A; Alkharfy, KM; Sanyal, A; Patel, TC; Chari, ST; Spaller, MR; Mukhopadhyay, D

Published Date

  • January 2014

Published In

Volume / Issue

  • 9 / 12

Start / End Page

  • e114409 -

PubMed ID

  • 25469510

Pubmed Central ID

  • 25469510

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0114409

Language

  • eng