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

Mohammad Islam, Arwa Alghamdi, Priyanka Sriramula, Basher Shalgm, Sarah Jones, Ian Ellis

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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
Publication statusPublished - 26 Nov 2018


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

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