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

HAKAMI, F., DARDA, L., STAFFORD, Prachi, WOLL, P., LAMBERT, D.W. and HUNTER, K.D. (2014). The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC). British journal of cancer, 111 (4), 807-16.

[img]
Preview
PDF
bjc2014372.pdf - Published Version
Creative Commons Attribution Non-commercial Share Alike.

Download (1MB) | Preview
Open Access URL: https://www.nature.com/articles/bjc2014372 (Published version)
Link to published version:: https://doi.org/10.1038/bjc.2014.372

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 by 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.

Item Type: Article
Additional Information:

Advance online publication, July 10, 2014

Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomedical Research Centre
Identification Number: https://doi.org/10.1038/bjc.2014.372
Page Range: 807-16
Depositing User: Jamie Young
Date Deposited: 03 Jun 2015 12:41
Last Modified: 17 Mar 2021 20:16
URI: https://shura.shu.ac.uk/id/eprint/10003

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics