Open AccessFKBP51 regulates cell motility and invasion via RhoA signaling
Author(s) -
Takaoka Miho,
Ito Shun,
Miki Yoshio,
Nakanishi Akira
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13153
Subject(s) - rhoa , motility , fkbp , microbiology and biotechnology , downregulation and upregulation , cell , cytoskeleton , cell migration , biology , carcinogenesis , cancer research , cancer cell , signal transduction , chemistry , cancer , biochemistry , genetics , gene
FK 506 binding protein 51 ( FKBP 51), a member of the immunophilin family, is involved in multiple signaling pathways, tumorigenesis, and chemoresistance. FKBP 51 expression correlates with metastatic potential in melanoma and prostate cancer. However, the functions of FKBP 51, particularly involving the regulation of cell motility and invasion, are not fully understood. We discovered two novel interacting partner proteins of FKBP 51, i.e., deleted in liver cancer 1 ( DLC 1) and deleted in liver cancer 2 ( DLC 2), using immunoprecipitation and mass spectrometry. DLC 1 and DLC 2 are Rho GTP ase‐activating proteins that are frequently downregulated in various cancers. Next, we demonstrated that overexpression of FKBP 51 enhances cell motility and invasion of U 2 OS cells via upregulation of RhoA activity and enhanced Rho‐ ROCK signaling. Moreover, FKBP 51‐depleted cells displayed a cortical distribution of actin filaments and decreased cell motility and invasion. Consistent with this phenotype, FKBP 51 depletion caused a downregulation of RhoA activity. Considered together, our results demonstrate that FKBP 51 positively controls cell motility by promoting RhoA and ROCK activation; thus, we have revealed a novel role for FKBP 51 in cytoskeletal rearrangement and cell migration and invasion.