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PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-esophageal epithelium

Lookup NU author(s): Dr Ralf Kist, Dr Heiko Peters

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by John Wiley & Sons Ltd, 2018.

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Abstract

PAX9 is a transcription factor of the PAX family characterized by a DNA-binding paired domain. Previous studies have suggested a potential role of PAX9 in squamous cell differentiation and carcinogenesis of the oro-esophageal epithelium. However, its functional roles in differentiation and carcinogenesis remain unclear. In this study, Pax9 deficiency in the mouse esophagus promoted cell proliferation, delayed cell differentiation and altered the global gene expression profile. Ethanol exposure down-regulated PAX9 expression in human esophageal epithelial cells in vitro and mouse forestomach and tongue in vivo. We further showed that PAX9 was down-regulated in human oro-esophageal squamous cell carcinoma (OESCC), and its down-regulation was associated with alcohol drinking and promoter hypermethylation. Moreover, ad libitum feeding with a liquid diet containing ethanol for 40 weeks or Pax9 deficiency promoted N-nitrosomethylbenzylamine-induced squamous cell carcinogenesis in mouse tongue, esophagus, and forestomach. In conclusion, PAX9 regulates squamous cell differentiation in the oro-esophageal epithelium. Alcohol drinking and promoter hypermethylation are associated with PAX9 silencing in human OESCC. PAX9 down-regulation may contribute to alcohol-associated oro-esophageal squamous cell carcinogenesis.


Publication metadata

Author(s): Xiong Z, Ren S, Chen H, Liu Y, Huang C, Zhang YL, Odera JO, Chen T, Kist R, Peters H, Garman K, Sun Z, Chen X

Publication type: Article

Publication status: Published

Journal: Journal of Pathology

Year: 2018

Volume: 244

Issue: 2

Pages: 164-175

Print publication date: 01/02/2018

Online publication date: 21/10/2017

Acceptance date: 21/10/2017

Date deposited: 09/11/2017

ISSN (print): 0022-3417

ISSN (electronic): 1096-9896

Publisher: John Wiley & Sons Ltd

URL: https://doi.org/10.1002/path.4998

DOI: 10.1002/path.4998

PubMed id: 29055049


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