MAGIs: Junctional Scaffolds Linking Inter-Cellular Junction Architecture, Actin Cytoskeleton Dynamics, and Signaling Pathways

Abstract

MAGIs (membrane-associated guanylate-kinases (MAGUK) inverted) are apical scaffolds conserved across evolution, which regulate cellular junctions. Low expression of MAGIs has been associated with tumorigenesis in a wide variety of cancers. This "tumor-suppressive" function of MAGIs has stimulated many studies to better understand the processes they control, and how their misregulation could contribute to cancer progression. In this mini review, we will describe and discuss the recent advances concerning the role of MAGIs, and propose a potential framework to explain the link between the junctional role of MAGIs and the variety of signaling pathways found altered upon MAGIs loss in cancer cells. We argue that through the diversity of MAGIs' partners at the cell junctions, their impact on actin dynamics regulation, and the cellular contexts (other scaffolds or other actin regulators such as the AMOTs, NF2, etc.), the loss of MAGIs impacts different pathways, such as the PTEN/Akt, β-catenin, Hippo/YAP, or p38 pathways, to fuel tumorigenicity.