Targeting histone deacetylase and NFκB signaling as a novel therapy for Mucoepidermoid Carcinomas

Abstract

Malignancies from the salivary glands are rare and represent 11% of all cancers from the oropharyngeal anatomical area. Mucoepidermoid Carcinomas (MEC) is the most common malignancy from the salivary glands. Low survival rates of high-grade Mucoepidermoid Carcinomas (MEC) are particularly associated with the presence of positive lymph nodes, extracapsular lymph node spread, and perineural invasion. Most recently, the presence of cancer stem cells (CSC), and the activation of the NFκB signaling pathway have been suggested as cues for an acquired resistance phenotype. We have previously shown that NFκB signaling is very active in MEC tumors. Herein, we explore the efficacy of NFκB inhibition in combination with class I and II HDAC inhibitor to deplete the population of CSC and to destroy MEC tumor cells. Our finding suggests that disruption of NFκB signaling along with the administration of HDAC inhibitors constitute an effective strategy to manage MEC tumors.

Metadata

Item Type:	Article
Authors/Creators:	Wagner, V.P. https://orcid.org/0000-0002-1447-2135 Martins, M.D. Martins, M.A.T. Almeida, L.O. Warner, K.A. Nör, J.E. Squarize, C.H. Castilho, R.M. https://orcid.org/0000-0001-5358-612X
Copyright, Publisher and Additional Information:	© The Author(s) 2018. 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/.
Keywords:	Cell signalling; Targeted therapies
Dates:	Published: 1 February 2018 Published (online): 1 February 2018 Accepted: 15 January 2018
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	26 Jan 2023 15:27
Last Modified:	26 Jan 2023 15:27
Published Version:	http://dx.doi.org/10.1038/s41598-018-20345-w
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1038/s41598-018-20345-w
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:195653

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Targeting histone deacetylase and NFκB signaling as a novel therapy for Mucoepidermoid Carcinomas

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