American Association for Cancer Research
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Supplementary Figure 5 from Specific Cross-talk between Epidermal Growth Factor Receptor and Integrin αvβ5 Promotes Carcinoma Cell Invasion and Metastasis

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posted on 2023-03-30, 19:14 authored by Jill M. Ricono, Miller Huang, Leo A. Barnes, Steven K. Lau, Sara M. Weis, David D. Schlaepfer, Steven K. Hanks, David A. Cheresh
Supplementary Figure 5 from Specific Cross-talk between Epidermal Growth Factor Receptor and Integrin αvβ5 Promotes Carcinoma Cell Invasion and Metastasis

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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 αvβ5. 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 αvβ5 activation. This pathway induces αvβ5-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. [Cancer Res 2009;69(4):1383–91]