We have recently shown that the adaptor protein p140Cap regulates tumor properties in terms of cell motility and growth. Here, by using the highly metastatic rat adenocarcinoma cell line MTLn3-epidermal growth factor receptor (EGFR), we assess the role of p140Cap in metastasis formation. Orthotopic transplantation of MTLn3-EGFR cells over-expressing p140Cap in Rag2(-/-)γ(c)(-/-) mice resulted in normal primary tumor growth compared with the controls. Strikingly, p140Cap over-expression causes an 80\% inhibition in the number of lung metastases. p140Cap over-expressing cells display a 50\% reduction in directional cell migration, an increased number and size of focal adhesions, and a strong impairment in the ability to invade in a 3D matrix. p140Cap over-expression affects EGFR signaling and tyrosine phosphorylation of cortactin in response to EGF stimulation. Intriguingly, p140Cap associates with cortactin via interaction with its second proline-rich domain to the cortactin SH3 domain. The phosphomimetic cortactin tyrosine 421 mutant rescues migration and invasive properties in p140Cap over-expressing cells. Taken together, these data demonstrate that p140Cap suppresses the invasive properties of highly metastatic breast carcinoma cells by inhibiting cortactin-dependent cell motility.Oncogene advance online publication, 4 July 2011; doi:10.1038/onc.2011.257.

p140Cap suppresses the invasive properties of highly metastatic MTLn3-EGFR cells via impaired cortactin phosphorylation.

DAMIANO, Laura;DI STEFANO, PAOLA;REPETTO, DANIELE;DE LUCA, Elisa;TURCO, Emilia;DEFILIPPI, Paola
2012-01-01

Abstract

We have recently shown that the adaptor protein p140Cap regulates tumor properties in terms of cell motility and growth. Here, by using the highly metastatic rat adenocarcinoma cell line MTLn3-epidermal growth factor receptor (EGFR), we assess the role of p140Cap in metastasis formation. Orthotopic transplantation of MTLn3-EGFR cells over-expressing p140Cap in Rag2(-/-)γ(c)(-/-) mice resulted in normal primary tumor growth compared with the controls. Strikingly, p140Cap over-expression causes an 80\% inhibition in the number of lung metastases. p140Cap over-expressing cells display a 50\% reduction in directional cell migration, an increased number and size of focal adhesions, and a strong impairment in the ability to invade in a 3D matrix. p140Cap over-expression affects EGFR signaling and tyrosine phosphorylation of cortactin in response to EGF stimulation. Intriguingly, p140Cap associates with cortactin via interaction with its second proline-rich domain to the cortactin SH3 domain. The phosphomimetic cortactin tyrosine 421 mutant rescues migration and invasive properties in p140Cap over-expressing cells. Taken together, these data demonstrate that p140Cap suppresses the invasive properties of highly metastatic breast carcinoma cells by inhibiting cortactin-dependent cell motility.Oncogene advance online publication, 4 July 2011; doi:10.1038/onc.2011.257.
2012
2
624
633
http://dx.doi.org/10.1038/onc.2011.257
http://www.nature.com/onc/journal/vaop/ncurrent/pdf/onc2011257a.pdf
p140Cap; cortactin; tumor invasion; metastasis; breast cancer
Damiano L; Le Dévédec SE; Di Stefano P; Repetto D; Lalai R; Truong H; Xiong JL; Danen EH; Yan K; Verbeek FJ; De Luca E; Attanasio F; Buccione R; Turco E; van de Water B; Defilippi P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/92835
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