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.

Authors

• David 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

Publication/Presentation Date

6-1-2010

Abstract

The 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.

Volume

176

Issue

6

First Page

2997

Last Page

3006

ISSN

1525-2191

Published In/Presented At

Metalli, D., Lovat, F., Tripodi, F., Genua, M., Xu, S. Q., Spinelli, M., Alberghina, L., Vanoni, M., Baffa, R., Gomella, L. G., Iozzo, R. V., & Morrione, A. (2010). 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, 176(6), 2997–3006. https://doi.org/10.2353/ajpath.2010.090904

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

20395438

Department(s)

Administration and Leadership

Document Type

Article