N-cadherin as an invasion promoter: a novel target for antitumor therapy?

Cell adhesion molecules of the cadherin superfamily are frequently altered during tumor progression. The loss of E-cadherin, in particular, has long been described in various epithelial cancers where it correlates with malignancy and metastasis. In addition, a subset of tumors show de novo expression or upregulation of N-cadherin, a cadherin that promotes cell motility and invasion. In spite of the accumulating evidence supporting the relationship between N-cadherin levels and cancer progression, the causal role of N-cadherin in tumor development has not yet been clearly demonstrated. This review will address this issue at three different levels: (i) the expression pattern of N-cadherin in cancer; (ii) the cellular events that are modulated by N-cadherin and could account for its pro-invasive role in tumorigenesis; and (iii) the signaling properties of N-cadherin, with particular emphasis on its cross-talk with cell surface partners such as fibroblast growth factor receptor and with intracellular cascades such as the antiapoptotic machinery. Taken together, the topics discussed in this review point to N-cadherin as an important player in tumor development and, therefore, a potential target for novel therapeutic approaches.