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HOPX functions as a tumour suppressor in head and neck cancer

Lookup NU author(s): Dr Max RobinsonORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs. HOPX promoter methylation was observed in a subset of HNSCCs and was associated with a worse overall survival in HPV negative tumours. RNAseq analysis of OSCC cells transfected with HOPX revealed a widespread deregulation of the transcription of genes related to epithelial homeostasis and ectopic over-expression of HOPX in OSCC and NPC cells inhibited cell proliferation, plating efficiency and migration, and enhanced sensitivity to UVA-induced apoptosis. Our results demonstrate that HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis.


Publication metadata

Author(s): Yap LF, Lai SL, Patmanathan SN, Gokulan R, Robinson CM, White JB, Chai SJ, Rajadurai P, Prepageran N, Liew YT, Lopes V, Wei WB, Hollows RJ, Murray PG, Lambert DW, Hunter KD, Paterson IC

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2016

Volume: 6

Online publication date: 09/12/2016

Acceptance date: 14/11/2016

Date deposited: 28/02/2017

ISSN (print): 2045-2322

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/srep38758

DOI: 10.1038/srep38758


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Funding

Funder referenceFunder name
UM.C/625/1/HIR/MOHE/DENT/22University of Malaya-MOHE High Impact Research Grant

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