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

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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 PI3kinase and mTOR inhibitor, inhibited the phosphorylation of Akt and also effectively blocked VEGF-induced oral cancer cell motility, whereas only the PI3kinase 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.
Original languageEnglish
Pages (from-to)1294-1302
Number of pages9
JournalCellular Signalling
Volume26
Issue number6
Early online date19 Feb 2014
DOIs
Publication statusPublished - Jun 2014

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Mouth Neoplasms
Vascular Endothelial Growth Factor A
Cell Movement
Phosphorylation
Cell Line
Neoplasms
Head and Neck Neoplasms
Phosphatidylinositol 3-Kinases
Keratinocytes
Neck
Fibroblasts
Head

Keywords

  • VEGF
  • pAkt
  • Oral cancer
  • Cell migration

Cite this

@article{dced8afeccf24746b35bcc4c972f9786,
title = "Is there a pAkt between VEGF and oral cancer cell migration?",
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 PI3kinase and mTOR inhibitor, inhibited the phosphorylation of Akt and also effectively blocked VEGF-induced oral cancer cell motility, whereas only the PI3kinase 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 = "VEGF, pAkt, Oral cancer, Cell migration",
author = "Islam, {Mohammad R.} and Jones, {Sarah J.} and Michaelina Macluskey and Ellis, {Ian R.}",
note = "Copyright {\circledC} 2014. Published by Elsevier Inc.",
year = "2014",
month = "6",
doi = "10.1016/j.cellsig.2014.02.004",
language = "English",
volume = "26",
pages = "1294--1302",
journal = "Cellular Signalling",
issn = "0898-6568",
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TY - JOUR

T1 - Is there a pAkt between VEGF and oral cancer cell migration?

AU - Islam, Mohammad R.

AU - Jones, Sarah J.

AU - Macluskey, Michaelina

AU - Ellis, Ian R.

N1 - Copyright © 2014. Published by Elsevier Inc.

PY - 2014/6

Y1 - 2014/6

N2 - 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 PI3kinase and mTOR inhibitor, inhibited the phosphorylation of Akt and also effectively blocked VEGF-induced oral cancer cell motility, whereas only the PI3kinase 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.

AB - 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 PI3kinase and mTOR inhibitor, inhibited the phosphorylation of Akt and also effectively blocked VEGF-induced oral cancer cell motility, whereas only the PI3kinase 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.

KW - VEGF

KW - pAkt

KW - Oral cancer

KW - Cell migration

U2 - 10.1016/j.cellsig.2014.02.004

DO - 10.1016/j.cellsig.2014.02.004

M3 - Article

VL - 26

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JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

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ER -