The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC)

Show simple item record Hakami, Fahad Darda, Lav Stafford, Prachi Woll, Penella Lambert, Daniel W. Hunter, K.D. (Keith) 2014-09-08T10:00:23Z 2014-07
dc.description.abstract BACKGROUND : HOX gene expression is altered in many cancers; previous microarray revealed changes in HOX gene expression in head and neck squamous cell carcinoma (HNSCC), particularly HOXD10. METHODS : HOXD10 expression was assessed by qPCR and immunoblotting in vitro and b immunohistochemistry (IHC) in tissues. Low-expressing cells were stably transfected with HOXD10 and the phenotype assessed with MTS, migration and adhesion assays and compared with the effects of siRNA knockdown in high-HOXD10-expressing cells. Novel HOXD10 targets were identified using expression microarrays, confirmed by reporter assay, and validated in tissues using IHC. RESULTS : HOXD10 expression was low in NOKs, high in most primary tumour cells, and low in lymph node metastasis cells, a pattern confirmed using IHC in tissues. Overexpression of HOXD10 decreased cell invasion but increased proliferation, adhesion and migration, with knockdown causing reciprocal effects. There was no consistent effect on apoptosis. Microarray analysis identified several putative HOXD10-responsive genes, including angiomotin (AMOT-p80) and miR-146a. These were confirmed as HOXD10 targets by reporter assay. Manipulation of AMOT-p80 expression resulted in phenotypic changes similar to those on manipulation of HOXD10 expression. CONCLUSIONS : HOXD10 expression varies by stage of disease and produces differential effects: high expression giving cancer cells a proliferative and migratory advantage, and low expression may support invasion/metastasis, in part, by modulating AMOT-p80 levels. en_US
dc.description.librarian hb2014 en_US
dc.description.sponsorship Government of the Kingdom of Saudi Arabia en_US
dc.description.uri en_US
dc.identifier.citation Hakami, F, Darda, L, Stafford, P, Woll, P, Lambert, DW & Hunter, KD 2014, 'The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC)', British Journal of Cancer, vol. 111, no. 4, pp. 807-816. en_US
dc.identifier.issn 0007-0920 (print)
dc.identifier.issn 1532-1827 (online)
dc.identifier.other 10.1038/bjc.2014.372
dc.language.iso en en_US
dc.publisher Nature Publishing Group en_US
dc.rights © 2014 Cancer Research UK. All rights reserved 0007 – 0920/14 en_US
dc.subject HOX genes en_US
dc.subject HOXD10 en_US
dc.subject Head and neck en_US
dc.subject Metastasis en_US
dc.subject miR-146a en_US
dc.subject Head and neck squamous cell carcinoma (HNSCC) en_US
dc.subject Angiomotin (AMOT-p80) en_US
dc.title The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC) en_US
dc.type Postprint Article en_US

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