The Insulin-Like Growth Factor Receptor I Promotes Motility and Invasion of Bladder Cancer Cells through Akt- and Mitogen-Activated Protein Kinase-Dependent Activation of Paxillin
Gomella, Leonard G.
Iozzo, Renato V.
Permanent link to this recordhttp://hdl.handle.net/20.500.12613/7099
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AbstractThe insulin-like growth factor receptor I (IGF-IR) plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. Aberrant IGF-IR signaling is implicated in several types of tumors, including carcinomas of the lung, breast, prostate, pancreas, liver, and colon. However, the contribution of the IGF-IR to the development of the transformed phenotype in urothelial cells has not been clearly established. In this study we demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues compared with nonmalignant controls. We have investigated the role of the IGF-IR in bladder cancer by using urothelial carcinoma-derived 5637 and T24 cells. Although activation of the IGF-IR did not appreciably affect their growth, it did promote migration and stimulate in vitro wound closure and invasion. These effects required the activation of the Akt and Mitogen-activated protein kinase (MAPK) pathways as well as IGF-I-induced Akt- and MAPK-dependent phosphorylation of paxillin, which relocated at dynamic focal adhesions and was necessary for promoting motility in bladder cancer cells. Our results provide the first evidence for a role of the IGF-IR in motility and invasion of bladder cancer cells and support the hypothesis that the IGF-IR may play a critical role in the establishment of the invasive phenotype in urothelial neoplasia. Thus, the IGF-IR may also serve as a novel biomarker for bladder cancer.
CitationDavid Metalli, Francesca Lovat, Farida Tripodi, Marco Genua, Shi-Qiong Xu, Michela Spinelli, Lilia Alberghina, Marco Vanoni, Raffaele Baffa, Leonard G. Gomella, Renato V. Iozzo, Andrea Morrione, The Insulin-Like Growth Factor Receptor I Promotes Motility and Invasion of Bladder Cancer Cells through Akt- and Mitogen-Activated Protein Kinase-Dependent Activation of Paxillin, The American Journal of Pathology, Volume 176, Issue 6, 2010, Pages 2997-3006, ISSN 0002-9440, https://doi.org/10.2353/ajpath.2010.090904.
Citation to related workElsevier
Has partAmerican Journal of Pathology, Vol. 176, No. 6
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