Menin interacts with IQGAP1 to enhance intercellular adhesion of β-cells

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Abstract
Multiple endocrine neoplasia type 1 (MEN1) is a dominantly inherited tumor syndrome that results from the mutation of the MEN1 gene that encodes protein menin. Stable overexpression of MEN1 has been shown to partially suppress the Ras-mediated morphological changes of fibroblast cells. Little is known about the molecular mechanisms by which menin decreases the oncogenic effects on cell morphology and other phenotypes. Here we showed that ectopic expression of menin in pretumor β-cells increases islet cell adhesion and reduces cell migration. Our further studies revealed that menin interacts with the scaffold protein, IQ motif containing GTPase activating protein 1 (IQGAP1), reduces GTP–Rac1 interaction with IQGAP1 but increases epithelial cadherin (E-cadherin)/β-catenin interaction with IQGAP1. Consistent with an essential role for menin in regulating β-cell adhesion in vivo, accumulations of β-catenin and E-cadherin are reduced at cell junctions in the islets from Men1-excised mice. Together, these results define a novel menin–IQGAP1 pathway that controls cell migration and cell–cell adhesion in endocrine cells.