Cadherin Switching and Bladder Cancer

Purpose

Progression to or presentation with muscle invasive disease represents the critical clinical step in bladder cancer, necessitating more aggressive therapy and carrying a significantly worse survival rate. Bladder tumors typically show decreased expression of the cell-cell adhesion molecule E-cadherin as grade and stage progress, accompanied by increased expression of N-cadherin or P-cadherin in muscle invasive tumors. This phenomenon has been described as cadherin switching and may represent the key step in invasion. We introduce some of the concepts of cadherin mediated cell adhesion and biology, and describe cadherin switching in detail for bladder cancer.

Materials and Methods

We performed a PubMed® search for articles summarizing important concepts in cadherin biology and presenting primary evidence of cadherin expression in bladder cancer.

Results

Cadherin switching promotes a more malignant and invasive phenotype of bladder cancer in patients and laboratory based experimental systems. Bladder cancer is novel in that a switch to N-cadherin and P-cadherin expression occurs, although the precise timing and nature of this process remain unknown. Similarly the associated signaling pathways remain to be fully elucidated.

Conclusions

Cadherin switching is an important process late in the molecular pathogenesis of bladder cancer, and it may hold some of the answers to the development of muscle invasive and metastatic disease. Thus, the cadherin cell adhesion molecules represent strong candidate biological and molecular targets for preventing disease progression, and further investigation is warranted.

Key Words: urinary bladder neoplasms, cadherins, cell adhesion, cell biology

Abbreviations and Acronyms: CS, cadherin switching, EMT, epithelial-to-mesenchymal transition, FGF, fibroblast growth factor, GSK3β, glycogen synthase kinase-3β, MMP, matrix metalloproteinase, UC, urothelial carcinoma