Locking Src/Abl tyrosine kinase activities regulate cell differentiation and invasion of human cervical cancer cells expressing E6/E7 oncoproteins of high-risk HPV
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Authors
Yasmeen, Amber
Alachkar, Amal
Dekhil, Hafedh
Gambacorti-Passerin, Carlo
Moustafa, Ala-Eddin Al
Issue Date
2010-08-25
Type
Article
Language
en_US
Keywords
Src/Abl Tyrosine Kinase , Cell Differentiation , Human Cervical Cancer Cells , E6/E7 Oncoproteins , HPV
Alternative Title
Abstract
In this study, we compared the effects of SKI-606 with Iressa, Src/Abl and EGF-R kinase inhibitors, respectively, on selected parameters in HeLa and SiHa cervical cancer cell lines, which express E6/E7 oncoproteins of high-risk HPV types 18 and 16, respectively. Our results show that SKI-606 and Iressa inhibit cell proliferation and provoke G0-G1 cell cycle arrest and reduction of S and G2-M phase using 2 and 5 μM concentrations of these inhibitors. In contrast, SKI-606 induces differentiation to an epithelial phenotype “mesenchymal-epithelial transition”; thus SKI-606 causes a dramatic decrease in cell motility and invasion abilities of HeLa and SiHa cancer cells, in comparison to untreated cells and Iressa-treated cells in which these parameters are only slightly affected. These changes are accompanied by a regulation of the expression patterns of E-cadherin and catenins. The molecular pathway analysis of Src/Abl inhibitor revealed that SKI-606 blocks the phosphorylation of β-catenin and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule. Our findings indicate that SKI-606 inhibits signaling pathways involved in regulating tumor cell migration and invasion genes via β-catenin alteration, suggesting that Src inhibitor, in comparison to EGF-R, is a promising therapeutic agent for human cervical cancer.
Description
Citation
Yasmeen, A., Alachkar, A., Dekhil, H., Gambacorti-Passerini, C., & Al Moustafa, A. E. (2010). Locking Src/Abl Tyrosine Kinase Activities Regulate Cell Differentiation and Invasion of Human Cervical Cancer Cells Expressing E6/E7 Oncoproteins of High-Risk HPV. Journal of oncology, 2010, 530130. https://doi.org/10.1155/2010/530130
Publisher
Journal of Oncology