Specific Cross-talk between Epidermal Growth Factor Receptor and Integrin αvβ5 Promotes Carcinoma Cell Invasion and Metastasis
Year: 2009
Type: article
Abstract: 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.
Source: Cancer Research
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1230808483, Role of FAK in Tumorigenesis, G197287401, Integrin alpha v beta 3 promotes resistance to EGF receptor inhibitors, FAK/Src/CAS Signaling in Cell Motility and Invasion, G4753194685, Blood System in Coagulation and Vessel Disease, VEGF and PDGF in angiogenesis and tumor progression, Combinatorial Chemistry and Cancer Target, G6913420947, G711417664
OpenAlex ID: W2144398239