The motogenic effect of EGF and TGF-α on the migration of tumor cells from the oral region

Islam,; Mane, Shraddha; Hyder, Erum; Jones, Sarah; Ellis, Ian R.

doi:10.1177/2057178x17698481

Cited by 2 publications

(2 citation statements)

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“…Cell scattering is a dynamic process for investigating EMT in which dispersion of compact colonies of epithelial cells is induced by certain soluble factors such as growth factors [20]. The assay was performed as described earlier [10]. In brief, cells were seeded at a density of 2 × 10 4 cells/ml, in 60 mm dishes and grown until small well-defined colonies were visible.…”

Section: Scatter Assay and Immunofluorescent Stainingmentioning

confidence: 99%

“…We have previously shown that the PI3 kinase/Akt pathways are essential for the migration of fibroblasts and oral cancer cells in response to added factors. The addition of PI3 kinase/Akt inhibitors block the migration stimulating activity of VEGF, EGF and TGFα, the data indicating that those growth factors increase phosphorylation of Akt at Thr 308 and Ser 473 [8][9][10]. The role of TGFβ1, however, is still unknown in oral cancer cell metastasis.…”

Section: Introductionmentioning

confidence: 99%

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

Alghamdi¹,

Shalgm²,

Ellis³

et al. 2018

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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 TGFβ1induced 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.

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Section: Scatter Assay and Immunofluorescent Stainingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Alghamdi¹,

Shalgm²,

Ellis³

et al. 2018

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Receptor, Signal, Nucleus, Action: Signals That Pass through Akt on the Road to Head and Neck Cancer Cell Migration

Alzawi

Iftikhar

Shalgm

et al. 2022

Cancers

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This review aims to provide evidence for the role of the tumour microenvironment in cancer progression, including invasion and metastasis. The tumour microenvironment is complex and consists of tumour cells and stromal-derived cells, in addition to a modified extracellular matrix. The cellular components synthesise growth factors such as EGF, TGFα and β, VEGF, and NGF, which have been shown to initiate paracrine signalling in head and neck cancer cells by binding to cell surface receptors. One example is the phosphorylation, and hence activation, of the signalling protein Akt, which can ultimately induce oral cancer cell migration in vitro. Blocking of Akt activation by an inhibitor, MK2206, leads to a significant decrease, in vitro, of cancer-derived cell migration, visualised in both wound healing and scatter assays. Signalling pathways have therefore been popular targets for the design of chemotherapeutic agents, but drug resistance has been observed and is related to direct tumour–tumour cell communication, the tumour–extracellular matrix interface, and tumour–stromal cell interactions. Translation of this knowledge to patient care is reliant upon a comprehensive understanding of the complex relationships present in the tumour microenvironment and could ultimately lead to the design of efficacious treatment regimens such as targeted therapy or novel therapeutic combinations.

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The motogenic effect of EGF and TGF-α on the migration of tumor cells from the oral region

Cited by 2 publications

References 43 publications

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

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

Receptor, Signal, Nucleus, Action: Signals That Pass through Akt on the Road to Head and Neck Cancer Cell Migration

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