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POU2F1 activity regulates HOXD10 and HOXD11 promoting a proliferative and invasive phenotype in head and neck cancer

Sharpe, Daniel J.; Orr, Katy S.; Moran, Michael; White, Sharon J.; McQuaid, Stephen; Lappin, Terence R.; Thompson, Alexander; James, Jacqueline A.

Authors

Daniel J. Sharpe

Katy S. Orr

Michael Moran

Sharon J. White

Stephen McQuaid

Terence R. Lappin

Jacqueline A. James



Abstract

HOX genes are master regulators of organ morphogenesis and cell differentiation during embryonic development, and continue to be expressed throughout post-natal life. To test the hypothesis that HOX genes are dysregulated in head and neck squamous cell carcinoma (HNSCC) we defined their expression profile, and investigated the function, transcriptional regulation and clinical relevance of a subset of highly expressed HOXD genes.

Two HOXD genes, D10 and D11, showed strikingly high levels in HNSCC cell lines, patient tumor samples and publicly available datasets. Knockdown of HOXD10 in HNSCC cells caused decreased proliferation and invasion, whereas knockdown of HOXD11 reduced only invasion.

POU2F1 consensus sequences were identified in the 5’ DNA of HOXD10 and D11. Knockdown of POU2F1 significantly reduced expression of HOXD10 and D11 and inhibited HNSCC proliferation. Luciferase reporter constructs of the HOXD10 and D11 promoters confirmed that POU2F1 consensus binding sites are required for optimal promoter activity.

Utilizing patient tumor samples a significant association was found between immunohistochemical staining of HOXD10 and both the overall and the disease-specific survival, adding further support that HOXD10 is dysregulated in head and neck cancer. Additional studies are now warranted to fully evaluate HOXD10 as a prognostic tool in head and neck cancers.

Journal Article Type Article
Publication Date Sep 16, 2014
Journal Oncotarget
Electronic ISSN 1949-2553
Publisher Impact Journals
Peer Reviewed Peer Reviewed
Volume 5
Issue 18
APA6 Citation Sharpe, D. J., Orr, K. S., Moran, M., White, S. J., McQuaid, S., Lappin, T. R., …James, J. A. (2014). POU2F1 activity regulates HOXD10 and HOXD11 promoting a proliferative and invasive phenotype in head and neck cancer. Oncotarget, 5(18), https://doi.org/10.18632/oncotarget.2492
DOI https://doi.org/10.18632/oncotarget.2492
Publisher URL http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=2492
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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