EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation.

Abstract:

:Tyrosine kinase receptors have an essential role in various aspects of tumor progression. In particular, epidermal growth factor receptor (EGFR) and its ligands have been implicated in the growth and dissemination of a wide array of human carcinomas. Here, we describe an EGFR-mediated signaling pathway that regulates human pancreatic carcinoma cell invasion and metastasis, yet does not influence the growth of primary tumors. In fact, ligation/activation of EGFR induces Src-dependent phosphorylation of two critical tyrosine residues of p130CAS, leading to the assembly of a Crk-associated substrate (CAS)/Nck1 complex that promotes Ras-associated protein-1 (Rap1) signaling. Importantly, GTP loading of Rap1 is specifically required for pancreatic carcinoma cell migration on vitronectin but not on collagen. Furthermore, Rap1 activation is required for EGFR-mediated metastasis in vivo without impacting primary tumor growth. These findings identify a molecular pathway that promotes the invasive/metastatic properties of human pancreatic carcinomas driven by EGFR.

journal_name

Oncogene

journal_title

Oncogene

authors

Huang M,Anand S,Murphy EA,Desgrosellier JS,Stupack DG,Shattil SJ,Schlaepfer DD,Cheresh DA

doi

10.1038/onc.2011.450

subject

Has Abstract

pub_date

2012-05-31 00:00:00

pages

2783-93

issue

22

eissn

0950-9232

issn

1476-5594

pii

onc2011450

journal_volume

31

pub_type

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