Interaction between membranous <scp>EBP50</scp> and myosin 9 as a favorable prognostic factor in ovarian clear cell carcinoma

  • Mayu Nakagawa
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan
  • Toshihide Matsumoto
    Department of Pathology Kitasato University School of Allied Health Science Sagamihara Japan
  • Ako Yokoi
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan
  • Miki Hashimura
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan
  • Yasuko Oguri
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan
  • Ryo Konno
    Center for Disease Proteomics, School of Science Kitasato University Sagamihara Japan
  • Yu Ishibashi
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan
  • Takashi Ito
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan
  • Kensuke Ohhigata
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan
  • Yohei Harada
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan
  • Naomi Fukagawa
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan
  • Yoshio Kodera
    Center for Disease Proteomics, School of Science Kitasato University Sagamihara Japan
  • Makoto Saegusa
    Department of Pathology Kitasato University School of Medicine Sagamihara Japan

書誌事項

公開日
2023-08-30
資源種別
journal article
権利情報
  • http://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1002/1878-0261.13503
公開者
Wiley

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説明

<jats:p>Ezrin‐radixin‐moesin‐binding phosphoprotein 50 (EBP50) is a scaffold protein that is required for epithelial polarity. Knockout (KO) of membranous EBP50 (Me‐EBP50) in ovarian clear cell carcinoma (OCCC) cells induced an epithelial–mesenchymal transition (EMT)‐like phenotype, along with decreased proliferation, accelerated migration capability, and induction of cancer stem cell (CSC)‐like properties. Shotgun proteomics analysis of proteins that co‐immunoprecipitated with EBP50 revealed that Me‐EBP50 strongly interacts with myosin 9 (MYH9). Specific inhibition of MYH9 with blebbistatin phenocopied Me‐EBP50 KO, and blebbistatin treatment potentiated the effects of Me‐EBP50 KO. In OCCC cells from clinical samples, Me‐EBP50 and MYH9 were co‐localized at the apical plasma membrane. Patients with a combination of Me‐EBP50‐high and MYH9‐high scores had the best prognosis for overall and progression‐free survival. Our data suggest that Me‐EBP50 has tumor‐suppressive effects through the establishment and maintenance of epithelial polarization. By contrast, loss of Me‐EBP50 expression induces EMT‐like phenotypes, probably due to MYH9 dysfunction; this results in increased cell mobility and enhanced CSC‐like properties, which in turn promote OCCC progression.</jats:p>

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