The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress

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 overexpres...

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Autores principales: Bhattacharya, Udayan, Thavathiru, Elangovan, Neizer-Ashun, Fiifi, Xu, Chao, Gatalica, Zoran, Dwivedi, Shailendra Kumar Dhar, Dey, Anindya, Mukherjee, Priyabrata, Bhattacharya, Resham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772324/
https://www.ncbi.nlm.nih.gov/pubmed/36543867
http://dx.doi.org/10.1038/s41698-022-00336-x
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author Bhattacharya, Udayan
Thavathiru, Elangovan
Neizer-Ashun, Fiifi
Xu, Chao
Gatalica, Zoran
Dwivedi, Shailendra Kumar Dhar
Dey, Anindya
Mukherjee, Priyabrata
Bhattacharya, Resham
author_facet Bhattacharya, Udayan
Thavathiru, Elangovan
Neizer-Ashun, Fiifi
Xu, Chao
Gatalica, Zoran
Dwivedi, Shailendra Kumar Dhar
Dey, Anindya
Mukherjee, Priyabrata
Bhattacharya, Resham
author_sort Bhattacharya, Udayan
collection PubMed
description 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.
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spelling pubmed-97723242022-12-23 The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress Bhattacharya, Udayan Thavathiru, Elangovan Neizer-Ashun, Fiifi Xu, Chao Gatalica, Zoran Dwivedi, Shailendra Kumar Dhar Dey, Anindya Mukherjee, Priyabrata Bhattacharya, Resham NPJ Precis Oncol Article 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. Nature Publishing Group UK 2022-12-21 /pmc/articles/PMC9772324/ /pubmed/36543867 http://dx.doi.org/10.1038/s41698-022-00336-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bhattacharya, Udayan
Thavathiru, Elangovan
Neizer-Ashun, Fiifi
Xu, Chao
Gatalica, Zoran
Dwivedi, Shailendra Kumar Dhar
Dey, Anindya
Mukherjee, Priyabrata
Bhattacharya, Resham
The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress
title The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress
title_full The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress
title_fullStr The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress
title_full_unstemmed The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress
title_short The deubiquitinase USP10 protects pancreatic cancer cells from endoplasmic reticulum stress
title_sort deubiquitinase usp10 protects pancreatic cancer cells from endoplasmic reticulum stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772324/
https://www.ncbi.nlm.nih.gov/pubmed/36543867
http://dx.doi.org/10.1038/s41698-022-00336-x
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