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
Oncogenejournal_title
Oncogeneauthors
Huang M,Anand S,Murphy EA,Desgrosellier JS,Stupack DG,Shattil SJ,Schlaepfer DD,Cheresh DAdoi
10.1038/onc.2011.450subject
Has Abstractpub_date
2012-05-31 00:00:00pages
2783-93issue
22eissn
0950-9232issn
1476-5594pii
onc2011450journal_volume
31pub_type
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