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.

Details

Title
Targeting histone deacetylase and NFκB signaling as a novel therapy for Mucoepidermoid Carcinomas
Author
Wagner, Vivian P 1   VIAFID ORCID Logo  ; Martins, Manoela D 1 ; Martins, Marco A T 2 ; Almeida, Luciana O 3 ; Warner, Kristy A 4 ; Nör, Jacques E 5 ; Squarize, Cristiane H 6 ; Castilho, Rogerio M 6   VIAFID ORCID Logo 

1  Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Experimental Pathology Unit, Clinics Hospital of Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil 
2  Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Experimental Pathology Unit, Clinics Hospital of Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil 
3  Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA 
4  Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA 
5  Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Otolaryngology, Medical School, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, Michigan, USA 
6  Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA 
Pages
1-11
Publication year
2018
Publication date
Feb 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-20345-w
ProQuest document ID
1993380636
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.