The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress

Udayan Bhattacharya; Elangovan Thavathiru; Fiifi Neizer-Ashun; Chao Xu; Zoran Gatalica; Shailendra Kumar Dhar Dwivedi; Anindya Dey; Priyabrata Mukherjee; Resham Bhattacharya

doi:10.1038/s41698-022-00336-x

npj Precision Oncology (Dec 2022)

The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress

Udayan Bhattacharya,
Elangovan Thavathiru,
Fiifi Neizer-Ashun,
Chao Xu,
Zoran Gatalica,
Shailendra Kumar Dhar Dwivedi,
Anindya Dey,
Priyabrata Mukherjee,
Resham Bhattacharya

Affiliations

Udayan Bhattacharya: Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center
Elangovan Thavathiru: Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center
Fiifi Neizer-Ashun: Department of Cell Biology, University of Oklahoma Health Sciences Center
Chao Xu: Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center
Zoran Gatalica: Department of Pathology, University of Oklahoma Health Sciences Center
Shailendra Kumar Dhar Dwivedi: Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center
Anindya Dey: Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center
Priyabrata Mukherjee: Department of Pathology, University of Oklahoma Health Sciences Center
Resham Bhattacharya: Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center

DOI: https://doi.org/10.1038/s41698-022-00336-x
Journal volume & issue: Vol. 6, no. 1
pp. 1 – 6

Abstract

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Abstract The ubiquitin-specific peptidase 10 (USP10) plays a context-specific, pro or anti-tumorigenic role in different malignancies. However, the role of USP10 in pancreatic cancer remains unclear. Our protein and RNA level analysis from archived specimens and public databases show that USP10 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and expression correlates with poor overall patient survival. Phenotypically, silencing USP10 decreased viability, clonal growth and invasive properties of pancreatic cancer cells. Mechanistically, silencing USP10 upregulated BiP and induced endoplasmic reticulum (ER) stress that led to an unfolded protein response (UPR) and upregulation of PERK, IRE1α. Decreased cell viability of USP10 silenced cells could be rescued by a chemical chaperone that promotes protein folding. Our studies suggest that USP10 by protecting pancreatic cancer cells from ER stress may support tumor progression.

Published in npj Precision Oncology

ISSN: 2397-768X (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.nature.com/npjprecisiononcology/

About the journal