The importance of integrin-linked kinase in the regulation of bladder cancer invasion.

Abstract

It is important to understand the molecular mechanisms of bladder cancer progression not only to prevent cancer progression but also to detect new therapeutic targets against advanced bladder cancer. The integrin-linked kinase (ILK) is a major signaling integrator in mammalian cells and plays an important role in epithelial-mesenchymal transition (EMT) of human cancers, but its mechanisms are not completely understood. In this study, we investigated the importance and mechanisms of ILK in bladder cancer progression. When the expression of ILK in bladder cancer cell lines and N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced murine bladder cancer was evaluated, ILK has a tendency to be overexpressed in invasive cell lines and invasive BBN-induced murine bladder cancer. Overexpression of ILK in 253J bladder cancer cells suppressed E-cadherin expression, resulting in the promotion of cell invasion. Conversely, ILK knockdown by siRNA suppresses cell invasion in invasive bladder cancer cells through the regulation of E-cadherin or matrix metalloprotease 9 (MMP-9). To regulate E-cadherin expression, our results showed that the glycogen synthase kinase 3β (GSK3β)-Zeb1 pathway may play an important role downstream of ILK. Finally, the results of a human bladder tissue microarray (TMA) showed that ILK expression correlates with the invasiveness of human bladder cancer. Our study suggests that ILK is overexpressed in invasive bladder cancer and plays an important role in the EMT of bladder cancer via the control of E-cadherin and MMP-9 expression. ILK may be a new molecular target to suppress tumor progression in advanced and high-risk bladder cancer patients.

• Authors: Yoshiyuki Matsui, Kiran Assi, Osamu Ogawa, Peter A Raven, Shoukat Dedhar, Martin E Gleave, Baljinder Salh, Alan I So
• Journal: International journal of cancer (Int J Cancer) Vol. 130 Issue 3 Pg. 521-31 (Feb 01 2012) ISSN: 1097-0215 [Electronic] United States
• PMID: 21351095 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 UICC.

Chemical References

• Cadherins
• integrin-linked kinase
• Protein Serine-Threonine Kinases
• Matrix Metalloproteinase 9

Topics

• Animals
• Cadherins (genetics, metabolism)
• Cell Line, Transformed
• Cell Line, Tumor
• Disease Models, Animal
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Humans
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Neoplasm Invasiveness (genetics)
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Urinary Bladder Neoplasms (enzymology, genetics, pathology)