Specific cross-talk between epidermal growth factor receptor and integrin alphavbeta5 promotes carcinoma cell invasion and metastasis.

Ricono JM, Huang M, Barnes LA, Lau SK, Weis SM, Schlaepfer DD, Hanks SK, Cheresh DA
Cancer Res. 2009 69 (4): 1383-91

PMID: 19208836 · PMCID: PMC2741736 · DOI:10.1158/0008-5472.CAN-08-3612

Tyrosine kinase receptors and integrins play essential roles in tumor cell invasion and metastasis. Previously, we showed that epidermal growth factor (EGF) stimulation of pancreatic carcinoma cells led to invasion and metastasis that was blocked by antagonists of integrin alpha(v)beta(5). Here, we show that EGF stimulates metastasis of carcinoma cells via a Src-dependent phosphorylation of p130 CAS leading to activation of Rap1, a small GTPase involved in integrin activation. Specifically, EGF receptor (EGFR)-induced Src activity leads to phosphorylation of a region within the CAS substrate domain, which is essential for Rap1 and alpha(v)beta(5) activation. This pathway induces alpha(v)beta(5)-mediated invasion and metastasis in vivo yet does not influence primary tumor growth or activation of other integrins on these cells. These findings show cross-talk between a tyrosine kinase receptor and an integrin involved in carcinoma cell invasion and metastasis and may explain in part how inhibitors of EGFR affect malignant disease.

MeSH Terms (21)

Animals Carcinoma Cell Movement Chick Embryo DNA Primers Epidermal Growth Factor ErbB Receptors Gene Knockdown Techniques Humans Inverted Repeat Sequences Lung Lung Neoplasms Mutation Neoplasm Invasiveness Neoplasm Metastasis Pancreatic Neoplasms Polymerase Chain Reaction Receptor Cross-Talk Receptors, Vitronectin RNA, Neoplasm Tumor Cells, Cultured

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