| Autor: |
Hsu CY; Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan.; Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan., Li JY; Institute of Molecular Biology, National Chung Hsing University, Taichung 402, Taiwan., Yang EY; Institute of Molecular Biology, National Chung Hsing University, Taichung 402, Taiwan., Liao TL; Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.; Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan., Wen HW; Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan., Tsai PC; Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.; Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan., Ju TC; Institute of Molecular Biology, National Chung Hsing University, Taichung 402, Taiwan., Lye LF; Department of Medical Research, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan., Nielsen BL; Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA., Liu HJ; Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.; Institute of Molecular Biology, National Chung Hsing University, Taichung 402, Taiwan.; Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.; The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. |
| Abstrakt: |
To explore whether the p17 protein of oncolytic avian reovirus (ARV) mediates cell migration and invadopodia formation, we applied several molecular biological approaches for studying the involved cellular factors and signal pathways. We found that ARV p17 activates the p53/phosphatase and tensin homolog (PTEN) pathway to suppress the focal adhesion kinase (FAK)/Src signaling and downstream signal molecules, thus inhibiting cell migration and the formation of invadopodia in murine melanoma cancer cell line (B16-F10). Importantly, p17-induced formation of invadopodia could be reversed in cells transfected with the mutant PTEN C124A . p17 protein was found to significantly reduce the expression levels of tyrosine kinase substrate 5 (TKs5), Rab40b, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1), and matrix metalloproteinases (MMP9), suggesting that TKs5 and Rab40b were transcriptionally downregulated by p17. Furthermore, we found that p17 suppresses the formation of the TKs5/NCK1 complex. Coexpression of TKs5 and Rab40b in B16-F10 cancer cells reversed p17-modulated suppression of the formation of invadopodia. This work provides new insights into p17-modulated suppression of invadopodia formation by activating the p53/PTEN pathway, suppressing the FAK/Src pathway, and inhibiting the formation of the TKs5/NCK1 complex. |
