This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Folgiero, V. Articles by Mercurio, A. M. Search for Related Content PubMed PubMed Citation Articles by Folgiero, V. Articles by Mercurio, A. M.

The ₆ß₄ Integrin Can Regulate ErbB-3 Expression: Implications for ₆ß₄ Signaling and Function

¹ Molecular Oncogenesis Laboratory, Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy; ² Department of Pathology, Duke University Medical Center, Durham, North Carolina; and ³ Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts

Requests for reprints: Rita Falcioni, Molecular Oncogenesis Laboratory, Department of Experimental Oncology, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy. Phone: 39-06-5266-2535; Fax: 39-06-5266-2505; E-mail: falcioni{at}ifo.it.

The integrin ₆ß₄ has been shown to facilitate key functions of carcinoma cells, including their ability to migrate, invade, and evade apoptosis. The mechanism involved seems to be a profound effect of ₆ß₄ on specific signaling pathways, especially the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. An intimate relationship between ₆ß₄ and growth factor receptors may explain this effect of ₆ß₄ on signaling. Previously, we showed that ₆ß₄ and ErbB-2 can function synergistically to activate the PI3K/Akt pathway. Given that ErbB-2 can activate PI3K only when it heterodimerizes with other members of the epidermal growth factor receptor family, these data imply that other receptors cooperate in this process. Here, we report that ₆ß₄ can regulate the expression of ErbB-3 using several different models and that the consequent formation of an ErbB-2/ErbB-3 heterodimer promotes the ₆ß₄-dependent activation of PI3K/Akt and the ability of this integrin to impede apoptosis of carcinoma cells. Our data also support the hypothesis that ₆ß₄ can regulate ErbB-3 expression at the translational level as evidenced by the findings that ₆ß₄ does not increase ErbB-3 mRNA significantly, and that this regulation is both rapamycin sensitive and dependent on eukaryotic translation initiation factor 4E. These findings provide one mechanism to account for the activation of PI3K by ₆ß₄ and they also provide insight into the regulation of ErbB-3 in carcinoma cells. [Cancer Res 2007;67(4):1645–52]

This article has been cited by other articles:

				P. Dentelli, A. Rosso, A. Zeoli, R. Gambino, L. Pegoraro, G. Pagano, R. Falcioni, and M. F. Brizzi Oxidative Stress-mediated Mesangial Cell Proliferation Requires RAC-1/Reactive Oxygen Species Production and beta4 Integrin Expression J. Biol. Chem., September 7, 2007; 282(36): 26101 - 26110. [Abstract] [Full Text] [PDF]