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

Academic Article

Abstract

  • © 2014 Bhattacharya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.
  • Authors

    Published In

  • PLoS ONE  Journal
  • Digital Object Identifier (doi)

    Author List

  • Bhattacharya S; Pal K; Sharma AK; Dutta SK; Lau JS; Yan IK; Wang E; Elkhanany A; Alkharfy KM; Sanyal A
  • Volume

  • 9
  • Issue

  • 12