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Interaction between membranous <scp>EBP50</scp> and myosin 9 as a favorable prognostic factor in ovarian clear cell carcinoma
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- Makoto Saegusa
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Yasuko Oguri
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Mayu Nakagawa
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Ako Yokoi
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Takashi Ito
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Toshihide Matsumoto
- Department of Pathology Kitasato University School of Allied Health Science Sagamihara Japan
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- Miki Hashimura
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Yohei Harada
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Yu Ishibashi
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Ryo Konno
- Center for Disease Proteomics, School of Science Kitasato University Sagamihara Japan
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- Kensuke Ohhigata
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Naomi Fukagawa
- Department of Pathology Kitasato University School of Medicine Sagamihara Japan
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- Yoshio Kodera
- Center for Disease Proteomics, School of Science Kitasato University Sagamihara Japan
Bibliographic Information
- Published
- 2023-08-30
- Resource Type
- journal article
- Rights Information
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- http://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.1002/1878-0261.13503
- Publisher
- Wiley
Search this article
Description
<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>
Journal
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- Molecular Oncology
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Molecular Oncology 17 (10), 2168-2182, 2023-08-30
Wiley

