We recently reported that the adaptor protein p140Cap affects tumour properties of cancer cells interfering with Src kinase activity and downstream signalling. Here we describe that p140Cap stabilizes adherens junctions and inhibits epidermal growth factor receptor (EGFR) signalling, blocking scatter and proliferation of cancer cells. p140Cap regulates these events through a dual mechanism, involving both inhibition of c-Src kinase and up-regulation of RasGAP activity. Interestingly, p140Cap expression is lost in more aggressive human breast cancers, showing an inverse correlation with EGFR expression. Thus, we provide evidences that p140Cap acts on the immobilisation of E-cadherin at the cell membrane and down-regulation of EGF receptor signalling, affecting crucial cancer properties such as growth and invasion.

p140Cap dual regulation of E-cadherin/EGFR cross-talk and Ras signalling in tumour cell scatter and proliferation

DAMIANO, Laura;DI STEFANO, PAOLA;CABODI, Sara;SAPINO, Anna;CASTELLANO, ISABELLA;TURCO, Emilia;DEFILIPPI, Paola
2010

Abstract

We recently reported that the adaptor protein p140Cap affects tumour properties of cancer cells interfering with Src kinase activity and downstream signalling. Here we describe that p140Cap stabilizes adherens junctions and inhibits epidermal growth factor receptor (EGFR) signalling, blocking scatter and proliferation of cancer cells. p140Cap regulates these events through a dual mechanism, involving both inhibition of c-Src kinase and up-regulation of RasGAP activity. Interestingly, p140Cap expression is lost in more aggressive human breast cancers, showing an inverse correlation with EGFR expression. Thus, we provide evidences that p140Cap acts on the immobilisation of E-cadherin at the cell membrane and down-regulation of EGF receptor signalling, affecting crucial cancer properties such as growth and invasion.
29(25)
3677
3690
http://www.nature.com/onc/journal/v29/n25/abs/onc2010128a.html
cell motility; p140Cap; Ras; Src; tumour growth
Damiano L; Di Stefano P; Camacho Leal MP; Barba M; Mainiero F; Cabodi S; Tordella L; Sapino A; Castellano I; Canel M; Frame M; Turco E; Defilippi P
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/62824
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