Interaction between membranous EBP50 and myosin 9 as a favorable prognostic factor in ovarian clear cell carcinoma
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Molecular oncology - 17(2023), 10 vom: 18. Okt., Seite 2168-2182 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nakagawa, Mayu [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer stem cell |
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| Anmerkungen: |
Date Revised 07.10.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1002/1878-0261.13503 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EBP50 | |
| 650 | 4 | |a cancer stem cell | |
| 650 | 4 | |a epithelial-mesenchymal transition | |
| 650 | 4 | |a migration | |
| 650 | 4 | |a myosin 9 | |
| 650 | 4 | |a ovarian clear cell carcinoma | |
| 700 | 1 | |a Matsumoto, Toshihide |e verfasserin |4 aut | |
| 700 | 1 | |a Yokoi, Ako |e verfasserin |4 aut | |
| 700 | 1 | |a Hashimura, Miki |e verfasserin |4 aut | |
| 700 | 1 | |a Oguri, Yasuko |e verfasserin |4 aut | |
| 700 | 1 | |a Konno, Ryo |e verfasserin |4 aut | |
| 700 | 1 | |a Ishibashi, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Ito, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Ohhigata, Kensuke |e verfasserin |4 aut | |
| 700 | 1 | |a Harada, Yohei |e verfasserin |4 aut | |
| 700 | 1 | |a Fukagawa, Naomi |e verfasserin |4 aut | |
| 700 | 1 | |a Kodera, Yoshio |e verfasserin |4 aut | |
| 700 | 1 | |a Saegusa, Makoto |e verfasserin |4 aut | |
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