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.
Cavallaro
Ugo
U
IFOM-The FIRC Institute of Molecular Oncology, Via Adamello 16, 1-20139 Milan, Italy. ugo.cavallaro@ifom-ieo-campus.it
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015820:Cadherins / Q000378:metabolism* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*
D000970:Antineoplastic Agents; D015820:Cadherins