title: HOPX functions as a tumour suppressor in head and neck cancer.
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.
authors.affiliation: Department of Oral and Craniofacial Sciences and Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Lee Fah
authors.initials: LF
authors.lastname: Yap
authors.affiliation: Department of Oral and Craniofacial Sciences and Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sook Ling
authors.initials: SL
authors.lastname: Lai
authors.affiliation: Department of Oral and Craniofacial Sciences and Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sathya Narayanan
authors.initials: SN
authors.lastname: Patmanathan
authors.affiliation: Department of Oral and Craniofacial Sciences and Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Ravindran
authors.initials: R
authors.lastname: Gokulan
authors.affiliation: Centre for Oral Health Research, Newcastle University, Newcastle, NE2 4BW, United Kingdom.
authors.forename: C Max
authors.initials: CM
authors.lastname: Robinson
authors.affiliation: Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, S10 2TA, Unite Kingdom.
authors.forename: Joe B
authors.initials: JB
authors.lastname: White
authors.affiliation: Cancer Research Malaysia, Selangor, 47500 Subang Jaya, Malaysia.
authors.forename: San Jiun
authors.initials: SJ
authors.lastname: Chai
authors.affiliation: Subang Jaya Medical Centre, 47500 Subang Jaya, Malaysia.
authors.forename: Pathmanathan
authors.initials: P
authors.lastname: Rajadurai
authors.affiliation: Department of Otorhinolaryngology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Prepageran
authors.affiliation: Department of Otorhinolaryngology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Yew Toong
authors.initials: YT
authors.lastname: Liew
authors.affiliation: Department of Oral surgery, Edinburgh Postgraduate Dental Institute, University of Edinburgh, Edinburgh, EH3 9HA, United Kingdom.
authors.forename: Victor
authors.initials: V
authors.lastname: Lopes
authors.affiliation: Institute of Cancer and Genomic Studies, University of Birmingham, Birmingham, B15 2TT, United Kingdom.|Sheffield Institute of Translational Neuroscience, University of Sheffield, Sheffield, S10 2HQ, United Kingdom.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wei
authors.affiliation: Institute of Cancer and Genomic Studies, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hollows
authors.affiliation: Institute of Cancer and Genomic Studies, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Murray
authors.affiliation: Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, S10 2TA, Unite Kingdom.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Lambert
authors.affiliation: Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, S10 2TA, Unite Kingdom.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Hunter
authors.affiliation: Department of Oral and Craniofacial Sciences and Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Paterson
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004249:DNA Damage; D019175:DNA Methylation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C476884:HOPX protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins