Integrin trafficking and its role in cancer metastasis

Enhanced levels of expression of certain integrins, and a consequent increase in specific integrin signals, have been linked to cancer cell progression. Dysfunctional integrin signaling is thought to be involved, at least in part, in mediating the detachment of tumor cells from neighboring cells while providing enhanced survival and proliferative capabilities which allow such disseminating tumor cells to grow in new, foreign, microenvironments. Cell biologists have known for some time that integrin heterodimers are endocytosed from the plasma membrane in to the cytoplasm with some of this receptor later being exocytosed back to the cell surface; a cellular mechanism referred to as 'trafficking'. Although extensive research within the integrin field has elucidated key signal transduction pathways as being involved in integrin-mediated cellular behavior, both in normal and transformed cells, it is only relatively recently that the importance of integrin trafficking in modulating cellular function has been demonstrated. This review aims to identify the major trafficking molecules found to play a functional role in cancer cell behavior with special emphasis on the importance of integrin trafficking during neoplastic cell migration and invasion; vital components of the metastatic process.