Is it all just an Akt you’d be SMAD to believe it! Role of TGFβ1 in oral cancer metastasis

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Abstract

Introduction: TGFβ1 activates both SMAD and non-SMAD dependent signalling pathways but their role in oral cancer cell migration and metastasis is little known. The aim of this research was to investigate the role of TGFβ1-induced signalling pathways in oral cancer cell migration and to establish whether the inhibition of the associated pathway may be a suitable target for chemotherapeutic drug design to control oral cancer cell metastasis.
Materials and Methods: SDS-PAGE and Western blot techniques were used to investigate the expression and phosphorylation status of TGFβ1- induced key signalling molecules such as, SMAD, Akt and MAPK in normal keratinocytes and oral cancer cells. Gap closure and scatter assays were employed to study the effect of TGFβ1 on cell migration. Akt and MAPK inhibitors were also used to explore the role of associated signalling pathways in TGFβ1-induced cell migration. Phosphorylation of Akt, MAPK and SMAD were analysed by immunofluorescence in TGFβ1-induced migrated cells.
Results: TGFβ1 stimulated the phosphorylation of SMAD, Akt and MAPK in both normal keratinocytes and oral cancer cells. The level of phosphorylation, however, depended upon cell type, time of exposure to and concentration of TGFβ1. TGFβ1-stimulated cancer cell migration both as single cells (EMT, epithelial to mesenchymal transition) and as a sheet of cells. Inhibitor assays confirmed that cancer cell migration is phosphorylated-Akt dependent. However, TGFβ1 did not stimulate migration as a sheet of cells, but EMT of normal keratinocytes which was phosphorylated-MAPK dependent.
Conclusion: TGFβ1-induced oral cancer cell migration was dependent on the Akt signalling pathway. From this study, we propose that blocking the Akt pathway may inhibit oral cancer metastasis and could have potential in translating this research into clinical practice.

Original languageEnglish
Number of pages9
JournalDental Oral Biology and Craniofacial Research
Issue number3
DOIs
Publication statusPublished - 26 Nov 2018

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Mouth Neoplasms
Cell Movement
Neoplasm Metastasis
Keratinocytes
Phosphorylation
Epithelial-Mesenchymal Transition
Drug Design
Research
Fluorescent Antibody Technique
Polyacrylamide Gel Electrophoresis
Neoplasms
Western Blotting

Keywords

  • TGFβ1
  • Akt
  • SMAD
  • MAPK
  • oral cancer
  • cell migration
  • cell signalling

Cite this

@article{37913a9fad5849b79953b5686822db82,
title = "Is it all just an Akt you’d be SMAD to believe it!: Role of TGFβ1 in oral cancer metastasis",
abstract = "Introduction: TGFβ1 activates both SMAD and non-SMAD dependent signalling pathways but their role in oral cancer cell migration and metastasis is little known. The aim of this research was to investigate the role of TGFβ1-induced signalling pathways in oral cancer cell migration and to establish whether the inhibition of the associated pathway may be a suitable target for chemotherapeutic drug design to control oral cancer cell metastasis.Materials and Methods: SDS-PAGE and Western blot techniques were used to investigate the expression and phosphorylation status of TGFβ1- induced key signalling molecules such as, SMAD, Akt and MAPK in normal keratinocytes and oral cancer cells. Gap closure and scatter assays were employed to study the effect of TGFβ1 on cell migration. Akt and MAPK inhibitors were also used to explore the role of associated signalling pathways in TGFβ1-induced cell migration. Phosphorylation of Akt, MAPK and SMAD were analysed by immunofluorescence in TGFβ1-induced migrated cells.Results: TGFβ1 stimulated the phosphorylation of SMAD, Akt and MAPK in both normal keratinocytes and oral cancer cells. The level of phosphorylation, however, depended upon cell type, time of exposure to and concentration of TGFβ1. TGFβ1-stimulated cancer cell migration both as single cells (EMT, epithelial to mesenchymal transition) and as a sheet of cells. Inhibitor assays confirmed that cancer cell migration is phosphorylated-Akt dependent. However, TGFβ1 did not stimulate migration as a sheet of cells, but EMT of normal keratinocytes which was phosphorylated-MAPK dependent.Conclusion: TGFβ1-induced oral cancer cell migration was dependent on the Akt signalling pathway. From this study, we propose that blocking the Akt pathway may inhibit oral cancer metastasis and could have potential in translating this research into clinical practice.",
keywords = "TGFβ1, Akt, SMAD, MAPK, oral cancer, cell migration, cell signalling",
author = "Mohammad Islam and Arwa Alghamdi and Priyanka Sriramula and Basher Shalgm and Sarah Jones and Ian Ellis",
year = "2018",
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Is it all just an Akt you’d be SMAD to believe it! Role of TGFβ1 in oral cancer metastasis . / Islam, Mohammad; Alghamdi, Arwa; Sriramula, Priyanka ; Shalgm, Basher; Jones, Sarah; Ellis, Ian.

In: Dental Oral Biology and Craniofacial Research, No. 3, 26.11.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Is it all just an Akt you’d be SMAD to believe it!

T2 - Role of TGFβ1 in oral cancer metastasis

AU - Islam, Mohammad

AU - Alghamdi, Arwa

AU - Sriramula, Priyanka

AU - Shalgm, Basher

AU - Jones, Sarah

AU - Ellis, Ian

PY - 2018/11/26

Y1 - 2018/11/26

N2 - Introduction: TGFβ1 activates both SMAD and non-SMAD dependent signalling pathways but their role in oral cancer cell migration and metastasis is little known. The aim of this research was to investigate the role of TGFβ1-induced signalling pathways in oral cancer cell migration and to establish whether the inhibition of the associated pathway may be a suitable target for chemotherapeutic drug design to control oral cancer cell metastasis.Materials and Methods: SDS-PAGE and Western blot techniques were used to investigate the expression and phosphorylation status of TGFβ1- induced key signalling molecules such as, SMAD, Akt and MAPK in normal keratinocytes and oral cancer cells. Gap closure and scatter assays were employed to study the effect of TGFβ1 on cell migration. Akt and MAPK inhibitors were also used to explore the role of associated signalling pathways in TGFβ1-induced cell migration. Phosphorylation of Akt, MAPK and SMAD were analysed by immunofluorescence in TGFβ1-induced migrated cells.Results: TGFβ1 stimulated the phosphorylation of SMAD, Akt and MAPK in both normal keratinocytes and oral cancer cells. The level of phosphorylation, however, depended upon cell type, time of exposure to and concentration of TGFβ1. TGFβ1-stimulated cancer cell migration both as single cells (EMT, epithelial to mesenchymal transition) and as a sheet of cells. Inhibitor assays confirmed that cancer cell migration is phosphorylated-Akt dependent. However, TGFβ1 did not stimulate migration as a sheet of cells, but EMT of normal keratinocytes which was phosphorylated-MAPK dependent.Conclusion: TGFβ1-induced oral cancer cell migration was dependent on the Akt signalling pathway. From this study, we propose that blocking the Akt pathway may inhibit oral cancer metastasis and could have potential in translating this research into clinical practice.

AB - Introduction: TGFβ1 activates both SMAD and non-SMAD dependent signalling pathways but their role in oral cancer cell migration and metastasis is little known. The aim of this research was to investigate the role of TGFβ1-induced signalling pathways in oral cancer cell migration and to establish whether the inhibition of the associated pathway may be a suitable target for chemotherapeutic drug design to control oral cancer cell metastasis.Materials and Methods: SDS-PAGE and Western blot techniques were used to investigate the expression and phosphorylation status of TGFβ1- induced key signalling molecules such as, SMAD, Akt and MAPK in normal keratinocytes and oral cancer cells. Gap closure and scatter assays were employed to study the effect of TGFβ1 on cell migration. Akt and MAPK inhibitors were also used to explore the role of associated signalling pathways in TGFβ1-induced cell migration. Phosphorylation of Akt, MAPK and SMAD were analysed by immunofluorescence in TGFβ1-induced migrated cells.Results: TGFβ1 stimulated the phosphorylation of SMAD, Akt and MAPK in both normal keratinocytes and oral cancer cells. The level of phosphorylation, however, depended upon cell type, time of exposure to and concentration of TGFβ1. TGFβ1-stimulated cancer cell migration both as single cells (EMT, epithelial to mesenchymal transition) and as a sheet of cells. Inhibitor assays confirmed that cancer cell migration is phosphorylated-Akt dependent. However, TGFβ1 did not stimulate migration as a sheet of cells, but EMT of normal keratinocytes which was phosphorylated-MAPK dependent.Conclusion: TGFβ1-induced oral cancer cell migration was dependent on the Akt signalling pathway. From this study, we propose that blocking the Akt pathway may inhibit oral cancer metastasis and could have potential in translating this research into clinical practice.

KW - TGFβ1

KW - Akt

KW - SMAD

KW - MAPK

KW - oral cancer

KW - cell migration

KW - cell signalling

U2 - 10.31487/j.DOBCR.2018.03.004

DO - 10.31487/j.DOBCR.2018.03.004

M3 - Article

IS - 3

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