HOPX functions as a tumour suppressor in head and neck cancer

Sci Rep. 2016 Dec 9:6:38758. doi: 10.1038/srep38758.

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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • DNA Damage
  • DNA Methylation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Homeodomain Proteins / genetics*
  • Homeostasis
  • Humans
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • Squamous Cell Carcinoma of Head and Neck
  • Transcription, Genetic
  • Tumor Suppressor Proteins / genetics*

Substances

  • HOPX protein, human
  • Homeodomain Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins