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

22 Citations (Scopus)

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 1 2014

Fingerprint

exosomes
Exosomes
pancreatic neoplasms
autophagy
Autophagy
Metabolic Networks and Pathways
Protein C
Pancreatic Neoplasms
biochemical pathways
proteins
Cells
drug resistance
gemcitabine
Drug Resistance
Neoplasms
Physiological Stress
neoplasms
biogenesis
Secretory Pathway
Pharmaceutical Preparations

ASJC Scopus subject areas

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

Cite this

GAIP interacting protein C-Terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways. / Bhattacharya, Santanu; Pal, Krishnendu; Sharma, Anil K.; Dutta, Shamit K.; Lau, Julie S.; Yan, Irene K.; Wang, Enfeng; Elkhanany, Ahmed; Alkharfy, Khalid M.; Sanyal, Arunik; Patel, Tushar C; Chari, Suresh T; Spaller, Mark R.; Mukhopadhyay, Debabrata.

In: PLoS One, Vol. 9, No. 12, e114409, 01.12.2014.

Research output: Contribution to journalArticle

Bhattacharya, Santanu ; Pal, Krishnendu ; Sharma, Anil K. ; Dutta, Shamit K. ; Lau, Julie S. ; Yan, Irene K. ; Wang, Enfeng ; Elkhanany, Ahmed ; Alkharfy, Khalid M. ; Sanyal, Arunik ; Patel, Tushar C ; Chari, Suresh T ; Spaller, Mark R. ; Mukhopadhyay, Debabrata. / GAIP interacting protein C-Terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways. In: PLoS One. 2014 ; Vol. 9, No. 12.
@article{66b91978a5af4a38afbcd9616850c4b6,
title = "GAIP interacting protein C-Terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways",
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.",
author = "Santanu Bhattacharya and Krishnendu Pal and Sharma, {Anil K.} and Dutta, {Shamit K.} and Lau, {Julie S.} and Yan, {Irene K.} and Enfeng Wang and Ahmed Elkhanany and Alkharfy, {Khalid M.} and Arunik Sanyal and Patel, {Tushar C} and Chari, {Suresh T} and Spaller, {Mark R.} and Debabrata Mukhopadhyay",
year = "2014",
month = "12",
day = "1",
doi = "10.1371/journal.pone.0114409",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - GAIP interacting protein C-Terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways

AU - Bhattacharya, Santanu

AU - Pal, Krishnendu

AU - Sharma, Anil K.

AU - Dutta, Shamit K.

AU - Lau, Julie S.

AU - Yan, Irene K.

AU - Wang, Enfeng

AU - Elkhanany, Ahmed

AU - Alkharfy, Khalid M.

AU - Sanyal, Arunik

AU - Patel, Tushar C

AU - Chari, Suresh T

AU - Spaller, Mark R.

AU - Mukhopadhyay, Debabrata

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84938524825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938524825&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0114409

DO - 10.1371/journal.pone.0114409

M3 - Article

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e114409

ER -