Is it all just an Akt - you’d be SMAD to believe it! Role of TGF?1 in oral cancer metastasis

Published on Nov 26, 2018
· DOI :10.31487/J.DOBCR.2018.03.004
Arwa Alghamdi1
Estimated H-index: 1
,
Basher Shalgm1
Estimated H-index: 1
+ 3 AuthorsSarah J. Jones9
Estimated H-index: 9
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Abstract
Introduction: TGF?1 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 TGF?1-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 TGF?1- 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 TGF?1 on cell migration. Akt and MAPK inhibitors were also used to explore the role of associated signalling pathways in TGF?1-induced cell migration. Phosphorylation of Akt, MAPK and SMAD were analysed by immunofluorescence in TGF?1-induced migrated cells. Results: TGF?1 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 TGF?1. TGF?1-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, TGF?1 did not stimulate migration as a sheet of cells, but EMT of normal keratinocytes which was phosphorylated-MAPK dependent. Conclusion: TGF?1-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.
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#1Hanan Ahmed (Dund.: University of Dundee)
#2Arpa Ghoshal (Dund.: University of Dundee)
Last. Mohammad Islam (Dund.: University of Dundee)H-Index: 3
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The signalling pathways involved in metastasis of oral adenoid cancer cells (TYS) in response to cancer-associated fibroblasts (COM D24) and normal oral mucosal fibroblasts (MM1) was examined. Metastatic cell behaviour was observed by cell-scatter, 3-D-collagen gel migration, and 3-D-spheroid invasion assays. Akt (v-Akt murine thymoma viral oncogene), MAPK(Mitogen activated protein kinase), EGFR (Epidermal growth factor receptor), TGFβRI (Transforming growth factor beta receptor 1), and CXCR4 (C...
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Last. Mohammad Tanvir IslamH-Index: 2
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