Loading...
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
Metalli, David Lovat, Francesca Tripodi, Farida Genua, Marco Xu, Shi-Qiong Spinelli, Michela Alberghina, Lilia Vanoni, Marco Baffa, Raffaele Gomella, Leonard G.
Metalli, David
Lovat, Francesca
Tripodi, Farida
Genua, Marco
Xu, Shi-Qiong
Spinelli, Michela
Alberghina, Lilia
Vanoni, Marco
Baffa, Raffaele
Gomella, Leonard G.
Citations
Altmetric:
Genre
Journal article
Date
2010-12-16
Advisor
Committee member
Group
Department
Biology
Subject
Permanent link to this record
Collections
Research Projects
Organizational Units
Journal Issue
DOI
https://doi.org/10.2353/ajpath.2010.090904
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.
Description
Citation
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, 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 work
Elsevier
Has part
American Journal of Pathology, Vol. 176, No. 6
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu