Tyrosine phosphorylation of paxillin affects the metastatic potential of human osteosarcoma
Open Access
- 2 May 2005
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 24 (30), 4754-4764
- https://doi.org/10.1038/sj.onc.1208654
Abstract
To acquire information on signal alteration corresponding to the changes in metastatic potential, we analysed protein tyrosine phosphorylation of low- and high-metastatic human osteosarcoma HuO9 sublines, which were recently established as the first metastatic model of human osteosarcoma. Tyrosine phosphorylation of proteins around 60, 70, and 120–130 kDa was enhanced in high-metastatic sublines. Among these proteins, the protein around 70 kDa, which was most remarkably phosphorylated, was identified as paxillin, a scaffold protein in integrin signaling. Activity of Src family kinase correlated well with metastatic potential, and a Src family kinase inhibitor, PP2, not only abolished tyrosine phosphorylation of paxillin but also impaired the motility of high-metastatic sublines. The expression of paxillin was also elevated in high-metastatic sublines, and knocking down of paxillin expression by RNAi method resulted in attenuated motility of high-metastatic cells. We also demonstrated that the phosphorylated form of paxillin is essential for the migration-promoting effect in human osteosarcoma. These findings suggest that enhanced activity of Src family kinases and overexpression of paxillin synergistically contribute to the high metastatic potential of human osteosarcoma through the hyperphosphorylation of paxillin.Keywords
This publication has 32 references indexed in Scilit:
- A renaissance for SRCNature Reviews Cancer, 2004
- Cooperative Roles of Fyn and Cortactin in Cell Migration of Metastatic Murine MelanomaJournal of Biological Chemistry, 2003
- Frequent amplification and rearrangement of chromosomal bands 6p12‐p21 and 17p11.2 in osteosarcomaGenes, Chromosomes and Cancer, 2003
- High‐resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarraysGenes, Chromosomes and Cancer, 2003
- Localized suppression of RhoA activity by Tyr31/118-phosphorylated paxillin in cell adhesion and migrationThe Journal of cell biology, 2002
- Paxillin: a focal adhesion-associated adaptor proteinOncogene, 2001
- Src family kinases are required for integrin but not PDGFR signal transductionThe EMBO Journal, 1999
- Stimulation of the protein tyrosine kinase c-Yes but not c-Src by neurotrophins in human brain-metastatic melanoma cellsOncogene, 1998
- Direct Binding of C-terminal Region of p130 to SH2 and SH3 Domains of Src KinasePublished by Elsevier BV ,1996
- Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly.The Journal of cell biology, 1992