The adaptor protein p140Cap/SNIP is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase (Csk). Here, by gain and loss of function approaches in breast and colon cancer cells, we report that p140Cap immobilizes E-cadherin at the cell membrane and inhibits EGFR and Erk1/2 signalling, blocking scatter and proliferation of cancer cells. p140Cap-dependent regulation of E-cadherin/EGFR cross-talk and cell motility is due to the inhibition of Src kinase. However, rescue of Src activity is not sufficient to restore Erk1/2 phosphorylation and proliferation. Indeed, p140Cap also impairs Erk1/2 phosphorylation by affecting Ras activity, downstream to the EGFR. In conclusion, p140Cap stabilizes adherens junctions and inhibits EGFR and Ras signalling through the dual control of both Src and Ras activities, thus affecting crucial cancer properties such as invasion and growth. Interestingly, p140Cap expression is lost in more aggressive human breast cancers, showing an inverse correlation with EGFR expression. Therefore, p140Cap mechanistically behaves as a tumour suppressor that inhibits signalling pathways leading to aggressive phenotypes. Oncogene (2010) 29, 3677-3690; doi: 10.1038/onc.2010.128; published online 10 May 2010

p140Cap dual regulation of E-cadherin/EGFR cross-talk and Ras signalling in tumour cell scatter and proliferation / L., Damiano; P., Di Stefano; Mpc, Leal; Barba, Matteo; Mainiero, Fabrizio; S., Cabodi; L., Tordella; A., Sapino; I., Castellano; M., Canel; M., Frame; E., Turco; P., Defilippi. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 29:25(2010), pp. 3677-3690. [10.1038/onc.2010.128]

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

BARBA, MATTEO;MAINIERO, Fabrizio;
2010

Abstract

The adaptor protein p140Cap/SNIP is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase (Csk). Here, by gain and loss of function approaches in breast and colon cancer cells, we report that p140Cap immobilizes E-cadherin at the cell membrane and inhibits EGFR and Erk1/2 signalling, blocking scatter and proliferation of cancer cells. p140Cap-dependent regulation of E-cadherin/EGFR cross-talk and cell motility is due to the inhibition of Src kinase. However, rescue of Src activity is not sufficient to restore Erk1/2 phosphorylation and proliferation. Indeed, p140Cap also impairs Erk1/2 phosphorylation by affecting Ras activity, downstream to the EGFR. In conclusion, p140Cap stabilizes adherens junctions and inhibits EGFR and Ras signalling through the dual control of both Src and Ras activities, thus affecting crucial cancer properties such as invasion and growth. Interestingly, p140Cap expression is lost in more aggressive human breast cancers, showing an inverse correlation with EGFR expression. Therefore, p140Cap mechanistically behaves as a tumour suppressor that inhibits signalling pathways leading to aggressive phenotypes. Oncogene (2010) 29, 3677-3690; doi: 10.1038/onc.2010.128; published online 10 May 2010
2010
tumour growth; src; cell motility; ras; p140cap
01 Pubblicazione su rivista::01a Articolo in rivista
p140Cap dual regulation of E-cadherin/EGFR cross-talk and Ras signalling in tumour cell scatter and proliferation / L., Damiano; P., Di Stefano; Mpc, Leal; Barba, Matteo; Mainiero, Fabrizio; S., Cabodi; L., Tordella; A., Sapino; I., Castellano; M., Canel; M., Frame; E., Turco; P., Defilippi. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 29:25(2010), pp. 3677-3690. [10.1038/onc.2010.128]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/47988
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 29
  • Scopus 42
  • ???jsp.display-item.citation.isi??? 45
social impact