title: Loss of Dlg5 expression promotes the migration and invasion of prostate cancer cells via Girdin phosphorylation.
abstract: Dlg5 has been reported to participate in cancer progression; however, its role in prostate cancer still remains poorly understood. In this study, we demonstrate that Dlg5 is frequently downregulated in prostate cancer. We show here that Dlg5 is involved in the regulation of cell migration and cancer cell invasion. Knockdown of endogenous Dlg5 markedly increased prostate cancer cell migration and invasion. Our studies, for the first time, demonstrate the interaction between Dlg5 and Girdin, an actin-binding Akt substrate. Importantly, we found that levels of Akt-mediated Girdin phosphorylation (p-Girdin-Ser1416) are increased in Dlg5-depleted cells. Small interfering RNA directed against Girdin and wortmannin treatment, which was found to reduce Girdin phosphorylation, impaired the effect of Dlg5 depletion on cell migration. Taken together, our findings demonstrate that Dlg5 interacts with and inhibits the activity of Girdin, thereby suppressing the migration of prostate cancer cells.
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: L
authors.initials: L
authors.lastname: Tomiyama
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sezaki
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsuo
authors.affiliation: 1] Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan [2] Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kioka
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; C502451:CCDC88A protein, human; C114461:DLG5 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins; D000077191:Wortmannin