Afadin (AF6) in cancer progression: A multidomain scaffold protein with complex and contradictory roles

Adherens (AJ) and tight junctions (TJ) maintain cell-cell adhesions and cellular polarity in normal tissues. Afadin, a multi-domain scaffold protein, is commonly found in both adherens and tight junctions, where it plays both structural and signal-modulating roles. Afadin is a complex modulator of cellular processes implicated in cancer progression, including signal transduction, migration, invasion, and apoptosis. In keeping with the complexities associated with the roles of adherens and tight junctions in cancer, afadin exhibits both tumor suppressive and pro-metastatic functions. In this review, we will explore the dichotomous roles that afadin plays during cancer progression.