Regulation and involvement in cancer and pathological conditions of MAGI1, a tight junction protein.

Membrane-associated guanylate kinase with an inverted repeat member 1 (MAGI1), is a member of a family of proteins which are emerging as important in coupling the extracellular environment to intracellular signaling pathways and the cytoskeleton at synapses and tight junctions. Early studies described it as a scaffold protein localized at cell-cell junctions. Recently, MAGI1 was found to recruit various kinds of molecules via its PSD-95/Disks Large/Zonula Occludins (PDZ) domains to strengthen the junctional complex. There is an increasing body of evidence showing its involvement in receptor synaptic localization and the homeostasis of ion channels in the nervous system. Furthermore, evidence has accumulated to confirm the critical role of MAGI1 in regulating cell-cell contacts, which is always disrupted in tumor progression and is associated with invasiveness and metastasis. It has also been shown in vitro that the abnormal expression of MAGI1 influences the adhesion and invasiveness of cancer cells. Due to the presence of docking domains for PDZ-binding molecules, MAGI1 associates with a variety of molecules such as phosphatase and tensin homolog deleted on chromosome ten (PTEN), brain-specific angiogenesis inhibitor-1, β-catenin and the mouse homologue of the human NET1 DH domain protein. Pathway signaling analysis has indicated that MAGI1 is probably involved in many kinds of pathways especially the PTEN/Phosphatidylinositol-3 kinase/Akt pathway and the (Wg-Int)-β-catenin pathway which mediates intracellular functions. MAGI1 may therefore be a tumor suppressor and a therapy target for cancer and other diseases, although more in vitro and in vivo investigations are required. Copyright