HOPX functions as a tumour suppressor in head and neck cancer

Lee Fah Yap; Sook Ling Lai; Sathya Narayanan Patmanathan; Ravindran Gokulan; C Max Robinson; Joe B White; San Jiun Chai; Pathmanathan Rajadurai; Narayanan Prepageran; Yew Toong Liew; Victor Lopes; Wenbin Wei; Robert J Hollows; Paul G Murray; Daniel W Lambert; Keith D Hunter; Ian C Paterson

doi:10.1038/srep38758

HOPX functions as a tumour suppressor in head and neck cancer

Lee Fah Yap, Sook Ling Lai, Sathya Narayanan Patmanathan, Ravindran Gokulan, C Max Robinson, Joe B White, San Jiun Chai, Pathmanathan Rajadurai, Narayanan Prepageran, Yew Toong Liew, Victor Lopes, Wenbin Wei, Robert J Hollows, Paul G Murray, Daniel W Lambert, Keith D Hunter, Ian C Paterson

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

146 Downloads (Pure)

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.

Original language	English
Article number	38758
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep38758
Publication status	Published - 9 Dec 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/srep38758Licence: Creative Commons: Attribution (CC BY)

Yap_et_al_HOPX_functions_Scientific_ReportsFinal published version, 1.64 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

Yap, L. F., Lai, S. L., Patmanathan, S. N., Gokulan, R., Robinson, C. M., White, J. B., Chai, S. J., Rajadurai, P., Prepageran, N., Liew, Y. T., Lopes, V., Wei, W., Hollows, R. J., Murray, P. G., Lambert, D. W., Hunter, K. D., & Paterson, I. C. (2016). HOPX functions as a tumour suppressor in head and neck cancer. Scientific Reports, 6, Article 38758. https://doi.org/10.1038/srep38758

@article{e3a80403c2844180a76e7f7942dac4dd,

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.",

author = "Yap, {Lee Fah} and Lai, {Sook Ling} and Patmanathan, {Sathya Narayanan} and Ravindran Gokulan and Robinson, {C Max} and White, {Joe B} and Chai, {San Jiun} and Pathmanathan Rajadurai and Narayanan Prepageran and Liew, {Yew Toong} and Victor Lopes and Wenbin Wei and Hollows, {Robert J} and Murray, {Paul G} and Lambert, {Daniel W} and Hunter, {Keith D} and Paterson, {Ian C}",

year = "2016",

month = dec,

day = "9",

doi = "10.1038/srep38758",

language = "English",

volume = "6",

journal = "Scientific Reports",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - HOPX functions as a tumour suppressor in head and neck cancer

AU - Yap, Lee Fah

AU - Lai, Sook Ling

AU - Patmanathan, Sathya Narayanan

AU - Gokulan, Ravindran

AU - Robinson, C Max

AU - White, Joe B

AU - Chai, San Jiun

AU - Rajadurai, Pathmanathan

AU - Prepageran, Narayanan

AU - Liew, Yew Toong

AU - Lopes, Victor

AU - Wei, Wenbin

AU - Hollows, Robert J

AU - Murray, Paul G

AU - Lambert, Daniel W

AU - Hunter, Keith D

AU - Paterson, Ian C

PY - 2016/12/9

Y1 - 2016/12/9

N2 - 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.

AB - 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.

U2 - 10.1038/srep38758

DO - 10.1038/srep38758

M3 - Article

C2 - 27934959

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 38758

ER -

HOPX functions as a tumour suppressor in head and neck cancer

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this