title: mda-9/Syntenin protein positively regulates the activation of Akt protein by facilitating integrin-linked kinase adaptor function during adhesion to type I collagen.
abstract: The integrin-linked kinase (ILK)-PINCH1-α-parvin (IPP) complex functions as a signaling platform for integrins that modulates various cellular processes. ILK functions as a central adaptor for the assembly of IPP complex. We report here that mda-9/syntenin, a positive regulator of cancer metastasis, regulates the activation of Akt (also known as protein kinase B) by facilitating ILK adaptor function during adhesion to type I collagen (COL-I) in human breast cancer cells. COL-I stimulation induced the phosphorylation and plasma membrane translocation of Akt. Inhibition of mda-9/syntenin or expression of mutant ILK (E359K) significantly blocked the translocation of both ILK and Akt to the plasma membrane. mda-9/syntenin associated with ILK, and this association was increased at the plasma membrane by COL-I stimulation. Knockdown of mda-9/syntenin impaired COL-I-induced association of ILK with Akt and plasma membrane targeting of ILK-Akt complex. These results demonstrated that mda-9/syntenin regulates the activation of Akt by controlling the plasma membrane targeting of Akt via a mechanism that facilitates the association of Akt with ILK at the plasma membrane during adhesion to COL-I. On a striking note, inhibition of mda-9/syntenin impaired COL-I-induced plasma membrane translocation of the IPP complex and assembly of integrin β1-IPP signaling complexes. Thus, our study defines the role of mda-9/syntenin in ILK adaptor function and describes a new mechanism of mda-9/syntenin for regulation of cell migration.
authors.affiliation: Medical and Biomaterials Research Center and Department of Biochemistry, College of Natural Sciences, Kangwon National University Chuncheon 200-701, Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Hwangbo
authors.forename: Juhee
authors.initials: J
authors.lastname: Park
authors.forename: Jeong-Hyung
authors.initials: JH
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000268:Adhesiveness / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D024042:Collagen Type I / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D060588:LIM Domain Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D053676:Syntenins / Q000378:metabolism*; D000099200:Scaffold Protein ILK; D000096985:Calponins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D024042:Collagen Type I; D019012:Integrin beta1; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D053676:Syntenins; D000099200:Scaffold Protein ILK; C088088:LIMS1 protein, human; C486590:PARVA protein, human; D000096985:Calponins; C109621:SDCBP protein, human