Multitasking in tumor progression: Signaling functions of cell adhesion molecules

Approximately 90% of all cancer deaths arise from metastasis formation. Hence, understanding the molecular mechanisms underlying tumor progression, local invasion, and the formation of tumor metastases represents one of the great challenges in exploratory cancer research. Recent experimental results indicate that changes in cell adhesion play a critical role in tumor progression. Cell adhesion molecules of varying classes and functions, including cadherins, cell adhesion molecules of the immunoglobulin family (Ig-CAMs), CD44, and integrins, can interact with and modulate the signaling function of receptor tyrosine kinases (RTKs). Conversely, signaling by RTKs can directly affect the adhesive function of adhesion molecules. Loss of E-cadherin and gain of mesenchymal cadherin function as well as changes in the expression of Ig-CAMs during the progression of many cancer types exemplify such functional implicatons: cell adhesion molecules not only define a tumor cell's adhesive repertoire, but also directly influence classic signal transduction pathways, thereby modulating the metastatic behavior of tumor cells.