HOPX functions as a tumour suppressor in head and neck cancer
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Colleges, School and Institutes
- Department of Oral and Craniofacial Sciences and Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
- Newcastle University
- Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, S10 2TA, Unite Kingdom.
- Cancer Research Malaysia, Selangor, 47500 Subang Jaya, Malaysia.
- Subang Jaya Medical Centre, 47500 Subang Jaya, Malaysia.
- Department of Otorhinolaryngology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
- University of Edinburgh, The
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 status||Published - 9 Dec 2016|