1. PAK4, MCF-7 hücrelerinde E-kaderini baskýlayarak PKC-baðýmlý invaziv potansiyeli destekler.
- Author
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PEHLIVANOĞLU, Suray and AYDIN-ACAR, Çigdem
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PROTEIN kinase C , *CANCER cell migration , *CELL migration , *EPITHELIAL cells , *BREAST cancer - Abstract
Objective: The p21-activated kinase 4 (PAK4) overexpression is sufficient to initiate the tumorigenesis process in normal breast epithelial cells. Recent studies suggested that PAK4 could be an important oncogenic factor in breast cancer. The aim of this study was to investigate the migration ability of cells due to protein kinase C activation and inhibition and the expression levels of E-cadherin which provides cell-cell contact in MCF-7 breast cancer cells that PAK4 overexpressing and nonoverexpressing cells. Methods: MCF7 cell line was used as a breast cancer model. Ectopic expression of the wild-type human PAK4 gene was achieved using PAK4 plasmid in MCF7 cells. Plasmid p3XFLAG-CMV-10 was used as control vector. RO318220 was used as PKC inhibitor and phorbol 12-myristate-13-acetate (PMA / TPA) was used as PKC activator. Cells in both groups transfected with PAK4 plasmid and control vector were cultured for 0.2 h FBS, 10% FBS, RO318220 (5µM) and TPA (200 nM) for 48 hours. Cell migration in breast cancer cells was evaluated by Oris cell migration assay. Western blot method was used to evaluate the expression of E-cadherin. Results: It was determined that mesenchymallike phenotype was formed and the number and length of podosomal structures were increased in these PAK4 overexpressed cells. In addition, PKC activation via TPA treatment increased cell migration due to PAK4 overexpression. However, PKC-induced invasive effects were blocked by the PKC kinase inhibitor RO318220. In addition, PAK4 overexpression leads to downregulation of E-cadherin compared to control. Conclusion: E-cadherin is one of the basic structures that provide cell-cell contacts and prevent cell migration. Taken together, these findings suggest that PKC-activated PAK4 signalling contributes to breast cancer progression. Therefore, our results show that inhibition of the PKC-PAK4 signaling pathway may be a potential therapeutic approach for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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