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Article Dans Une Revue Molecular Biology Reports Année : 2023

Protein kinase D1 overexpression potentiates epidermal growth factor signaling pathway in MCF-7 cells

Christine Legay
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Sophie Doublier
Sylvie Babajko
Jean-Marc Ricort
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Résumé

Background Protein kinase D1, PKD1, is a serine-threonine kinase implicated in cell proliferation, migration, invasion, and/or apoptosis and its activation by several growth factors sets this enzyme as a key regulator of tumorigenesis and tumor progression. Despite many studies, its role in the regulation of intracellular signaling pathways remains widely disparate and needs to be clarified. Methods and results By using human breast cancer cells MCF-7, overexpressing or not PKD1, we demonstrated that PKD1 expression level modulated the tumor growth-promoting epidermal growth factor (EGF) signaling pathway. We also showed that EGF acutely stimulated PKD1 phosphorylation with similar time courses both in control and PKD1-overexpressing cells. However, PKD1 overexpression specifically and markedly increased EGF-induced phosphorylation of Akt (onto T308 and S473 residues) and extracellular-regulated protein kinase (ERK1/2). Finally, pharmacological inhibition of PKD1 activity or lowering its expression level using specific siRNAs drastically reduced EGF-stimulated Akt and ERK phosphorylation in PKD1overexpressing cells, but not in control cells. Conclusions Overall, these results identified the level of PKD1 expression as a key determinant in the regulation of the EGF signaling pathway highlighting its crucial role in a tumorigenic setting.
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Dates et versions

hal-04005896 , version 1 (28-02-2023)

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Christine Legay, Sophie Doublier, Sylvie Babajko, Jean-Marc Ricort. Protein kinase D1 overexpression potentiates epidermal growth factor signaling pathway in MCF-7 cells. Molecular Biology Reports, 2023, ⟨10.1007/s11033-023-08300-z⟩. ⟨hal-04005896⟩
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