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Cell Signal. 2014 Jun;26(6):1294-302. doi: 10.1016/j.cellsig.2014.02.004. Epub 2014 Feb 19.

Is there a pAkt between VEGF and oral cancer cell migration?

Author information

1
Unit of Cell & Molecular Biology, The Dental School, University of Dundee, Dundee DD1 4HN, UK.
2
Department of Oral Surgery and Medicine, The Dental School, University of Dundee, Dundee DD1 4HN, UK.
3
Unit of Cell & Molecular Biology, The Dental School, University of Dundee, Dundee DD1 4HN, UK. Electronic address: i.r.ellis@dundee.ac.uk.

Abstract

The PI3K-Akt signalling pathway is a well-established driver of cancer progression. One key process promoted by Akt phosphorylation is tumour cell motility; however the mechanism of VEGF-induced Akt phosphorylation leading to motility remains poorly understood. Previously, we have shown that Akt phosphorylation induced by different factors causes both stimulation and inhibition of motility in different cell types. However, differential phosphorylation of Akt at T308 and S473 residues by VEGF and its role in head and neck cancer cell motility and progression is unknown. The cell lines investigated in this study exhibited a change in phosphorylation of Akt in response to VEGF. However, in terms of motility, VEGF stimulated oral cancer and its associated cell lines, but not normal keratinocytes or oral mucosal fibroblasts. The addition of a PI3 kinase and mTOR inhibitor, inhibited the phosphorylation of Akt and also effectively blocked VEGF-induced oral cancer cell motility, whereas only the PI3 kinase inhibitor blocked oral cancer associated fibroblast cell motility. This study therefore discloses that two different mechanisms of Akt phosphorylation control the motility potential of different cell lines. Akt phosphorylated at both residues controls oral cancer cell motility. Furthermore, immunohistochemical analysis of VEGF positive human head and neck tumour tissues showed a significant increase in Akt phosphorylation at the T308 residue, suggesting that pAkt T308 may be associated with tumour progression in vivo.

KEYWORDS:

Cell migration; Oral cancer; VEGF; pAkt

PMID:
24561239
DOI:
10.1016/j.cellsig.2014.02.004
[Indexed for MEDLINE]

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