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

Santanu Bhattacharya, Krishnendu Pal, Anil K. Sharma, Shamit K. Dutta, Julie S. Lau, Irene K. Yan, Enfeng Wang, Ahmed Elkhanany, Khalid M. Alkharfy, Arunik Sanyal, Tushar C. Patel, Suresh T. Chari, Mark R. Spaller, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere114409
JournalPloS one
Volume9
Issue number12
DOIs
StatePublished - Dec 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Bhattacharya, S., Pal, K., Sharma, A. K., Dutta, S. K., Lau, J. S., Yan, I. K., Wang, E., Elkhanany, A., Alkharfy, K. M., Sanyal, A., Patel, T. C., Chari, S. T., Spaller, M. R., & Mukhopadhyay, D. (2014). GAIP interacting protein C-Terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways. PloS one, 9(12), [e114409]. https://doi.org/10.1371/journal.pone.0114409