MutY-Homolog (MYH) inhibition reduces pancreatic cancer cell growth and increases chemosensitivity

Sharbeen, G., Youkhana, J., Mawson, A., McCarroll, J., Nunez, A., Biankin, A. , Johns, A., Goldstein, D. and Phillips, P. (2016) MutY-Homolog (MYH) inhibition reduces pancreatic cancer cell growth and increases chemosensitivity. Oncotarget, 8(6), pp. 9216-9229. (doi:10.18632/oncotarget.13985) (PMID:27999205)

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Abstract

Patients with pancreatic ductal adenocarcinoma (PC) have a poor prognosis due to metastases and chemoresistance. PC is characterized by extensive fibrosis, which creates a hypoxic microenvironment, and leads to increased chemoresistance and intracellular oxidative stress. Thus, proteins that protect against oxidative stress are potential therapeutic targets for PC. A key protein that maintains genomic integrity against oxidative damage is MutY-Homolog (MYH). No prior studies have investigated the function of MYH in PC cells. Using siRNA, we showed that knockdown of MYH in PC cells 1) reduced PC cell proliferation and increased apoptosis; 2) further decreased PC cell growth in the presence of oxidative stress and chemotherapy agents (gemcitabine, paclitaxel and vincristine); 3) reduced PC cell metastatic potential; and 4) decreased PC tumor growth in a subcutaneous mouse model in vivo. The results from this study suggest MYH may be a novel therapeutic target for PC that could potentially improve patient outcome by reducing PC cell survival, increasing the efficacy of existing drugs and reducing metastatic spread.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Biankin, Professor Andrew
Authors: Sharbeen, G., Youkhana, J., Mawson, A., McCarroll, J., Nunez, A., Biankin, A., Johns, A., Goldstein, D., and Phillips, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncotarget
Publisher:Impact Journals
ISSN:1949-2553
ISSN (Online):1949-2553
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Oncotarget 8(6):9216-9229
Publisher Policy:Reproduced under a Creative Commons License

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