Menin interacts with IQGAP1 to enhance intercellular adhesion of beta-cells.
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 beta-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)/beta-catenin interaction with IQGAP1. Consistent with an essential role for menin in regulating beta-cell adhesion in vivo, accumulations of beta-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.
Yan
J
J
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Yang
Y
Y
Zhang
H
H
King
C
C
Kan
H-M
HM
Cai
Y
Y
Yuan
C-X
CX
Bloom
G S
GS
Hua
X
X
D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D016147:Genes, Tumor Suppressor; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051176:beta Catenin / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D015820:Cadherins; C101203:IQ motif containing GTPase activating protein 1; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D051176:beta Catenin; D020703:ras GTPase-Activating Proteins; D006160:Guanosine Triphosphate; D020830:rac1 GTP-Binding Protein