Epithelial-mesenchymal transition in lung cancer : Is tobacco the smoking gun ?

Over the last several years, epithelial-mesenchymal transition (EMT), a process in which cells undergo a switch from an epithelial phenotype to a mesenchymal phenotype, has emerged as important not only in embryonic development, but also as a potential mechanism for cancer progression. Epithelial cells are characterized by cell-cell interactions, with the formation of tight junctions, lateral, apical, and basal membranes, polarized distribution of cellular components, and lack of mobility, whereas mesenchymal cells have loose interaction with other cells, are not polarized, and can be motile. In order for a cell to undergo EMT, a number of dramatic cellular and molecular changes must take place. These changes include: dissolution of adherens junctions, reorganization of the actin cytoskeleton, loss of apical-basal polarity, induction of promesenchymal gene expression, and migration through basement membranes and tissues. In this review, we describe the molecular components that drive the transformation of normal cells to tumor cells, with an emphasis on the complex signaling networks that underlie EMT. We then examine how each of these players might mediate the transformation of lung epithelial cells induced by tobacco smoke.