期刊
ONCOGENE
卷 31, 期 22, 页码 2783-2793出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.450
关键词
pancreatic cancer; Rap1; CAS; EGFR; metastasis; tyrosine phosphorylation
资金
- NIH [CA107263, HL56595, HL47900, CA102310, CA045726]
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. Oncogene (2012) 31, 2783-2793; doi: 10.1038/onc.2011.450; published online 3 October 2011
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据