title: FKBP51 regulates cell motility and invasion via RhoA signaling.
abstract: FK506 binding protein 51 (FKBP51), a member of the immunophilin family, is involved in multiple signaling pathways, tumorigenesis, and chemoresistance. FKBP51 expression correlates with metastatic potential in melanoma and prostate cancer. However, the functions of FKBP51, particularly involving the regulation of cell motility and invasion, are not fully understood. We discovered two novel interacting partner proteins of FKBP51, i.e., deleted in liver cancer 1 (DLC1) and deleted in liver cancer 2 (DLC2), using immunoprecipitation and mass spectrometry. DLC1 and DLC2 are Rho GTPase-activating proteins that are frequently downregulated in various cancers. Next, we demonstrated that overexpression of FKBP51 enhances cell motility and invasion of U2OS cells via upregulation of RhoA activity and enhanced Rho-ROCK signaling. Moreover, FKBP51-depleted cells displayed a cortical distribution of actin filaments and decreased cell motility and invasion. Consistent with this phenotype, FKBP51 depletion caused a downregulation of RhoA activity. Considered together, our results demonstrate that FKBP51 positively controls cell motility by promoting RhoA and ROCK activation; thus, we have revealed a novel role for FKBP51 in cytoskeletal rearrangement and cell migration and invasion.
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Takaoka
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Japan.|Department of Genetic Diagnosis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakanishi
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D020690:GTPase-Activating Proteins; D034741:RNA, Small Interfering; D022021:Tacrolimus Binding Proteins; D025521:Tumor Suppressor Proteins; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000099159:Tacrolimus Binding Protein 5; C112352:DLC1 protein, human; C473607:STARD13 protein, human; C066737:RHOA protein, human
keywords: 
  ROCK
  ; Deleted in liver cancer 1; FKBP51; RhoA; deleted in liver cancer 2