Cooperative Roles of Fyn and Cortactin in Cell Migration of Metastatic Murine Melanoma

Huang, Jinhong; Asawa, Tamae; Takato, Tsuyoshi; Sakai, Ryuichi

doi:10.1074/jbc.m308213200

Cited by 65 publications

(61 citation statements)

References 34 publications

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“…Marchetti et al used brain metastatic sublines and found that kinase activity of Yes, not c-Src, was elevated compared to low-metastatic cells. We recently reported that, in a metastatic model of murine melanoma cell lines, kinase activity of Fyn was elevated in high-metastatic sublines, and interacted with cortactin (Huang et al, 2003). Although not as significant as in the case of murine melanoma, Fyn will also be a candidate for the responsible kinase for metastatic potential of human osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Tyrosine phosphorylation of paxillin affects the metastatic potential of human osteosarcoma

Azuma

Tanaka²,

Uekita³

et al. 2005

Oncogene

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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 highmetastatic 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 highmetastatic 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.

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Section: Discussionmentioning

confidence: 99%

Tyrosine phosphorylation of paxillin affects the metastatic potential of human osteosarcoma

Azuma

Tanaka²,

Uekita³

et al. 2005

Oncogene

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“…Cdc28 is the main CDK driving the cell cycle in budding yeast. Genetic interactions with checkpoint and APC mutants suggest Cdc28 may regulate checkpoint arrest downstream of the Budesonide-treated tumors also show decreased expression of the proto-oncogene Fyn, which is associated with tumor progression in cancer models including oral squamous cell carcinoma and metastatic murine melanoma (Huang et al, 2003;Li et al, 2003). This suggests a progressive phenotype for the It was recently reported that a combination treatment of dexamethasone and cisplatin on solid tumors of the lung and cervix resulted in less apoptosis compared with cisplatin alone (Herr et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Budesonide exerts its chemopreventive efficacy during mouse lung tumorigenesis by modulating gene expressions

Yao¹,

Wang²,

Lemon³

et al. 2004

Oncogene

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Budesonide, a glucocorticoid, was proven to be a highly effective agent in preventing the development of lung tumors in A/J mice. In a lung tumor bioassay, budesonide produced 70% inhibition of tumor multiplicity and 94% reduction of total tumor load compared to benzopyrene (B[a]P) treated mice. Gene expression array analysis was performed on mouse lung tumors from this bioassay using Affymetrix U74Av2 GeneChips to determine gene expression changes associated with budesonide treatment. We found 363 genes that were changed between lung tumors induced by treatment with B[a]P and similar tumors treated with budesonide. Among them, 243 genes were overexpressed and 120 genes were underexpressed after budesonide treatment. In addition, 108 genes differentially expressed during mouse lung tumorigenesis (50 genes overexpressed and 58 genes underexpressed) were modulated back to normal levels after budesonide treatment when compared with the controls group. These genes are involved in a broad range of different pathways including control of cell cycle, signal transduction, and apoptosis and may play a role in the observed preventive effect. Our results suggest that budesonide exerts its effects of chemoprevention through growth arrest via Mad2/3 and through apoptosis via Bim/Blk and, by inference, caspase-8/9. Using the pathway visualization tool GenMapp, G protein pathway and MAPK cascade were also regulated by budesonide. Thus, we have determined, for the first time, the expression profiles of genes modulated by budesonide during murine lung tumorigenesis. Our results indicate that the chemopreventive effects of budesonide in the mouse lung tumorigenesis assay involved increase and decrease expression of a wide variety of genes in multiple signaling pathways.

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“…Interplay between Src kinases and cortactin seems to be important particularly in cells of high metastatic potential (Li et al, 2001;Huang et al, 2003). Hence, activation of the cortactin-WIP-Arp2/3 pathway is likely an additional mechanism by which activated Src augments cell motility in a tumor.…”

Section: Role Of Cortactinmentioning

confidence: 99%

The interplay between Src and integrins in normal and tumor biology

2004

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Src family nonreceptor protein tyrosine kinases transduce signals that control normal cellular processes such as cell proliferation, adhesion and motility. Normally, cellular Src is held in an inactive state, but in several cancer types, abnormal events lead to elevated kinase activity of the protein and cause pleiotropic cellular responses inducing transformation and metastasis. A prerequisite of the ability of a cancer cell to undergo metastasis into distant tissues is to penetrate surrounding extracellular matrices. These processes are facilitated by the integrin family of cell adhesion molecules. As is the case with Src, altered integrin activity or substrate affinity can contribute to the neoplastic phenotype. Therefore, understanding the interplay between Src and integrin function has been of intense interest over the past few years. This review focuses on the role of Src and integrin signaling in normal cells and how this is deregulated in human cancer. We will identify the key players in the integrin-mediated signaling pathways involved in cell motility and apoptosis, such as FAK, paxillin and p130 CAS , and discuss how Src signaling affects the formation of focal adhesions and the extracellular matrix.

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Cooperative Roles of Fyn and Cortactin in Cell Migration of Metastatic Murine Melanoma

Cited by 65 publications

References 34 publications

Tyrosine phosphorylation of paxillin affects the metastatic potential of human osteosarcoma

Tyrosine phosphorylation of paxillin affects the metastatic potential of human osteosarcoma

Budesonide exerts its chemopreventive efficacy during mouse lung tumorigenesis by modulating gene expressions

The interplay between Src and integrins in normal and tumor biology

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