EBP50 Depletion and Nuclear β-Catenin Accumulation Engender Aggressive Behavior of Colorectal Carcinoma through Induction of Tumor Budding
Ezin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a scaffold protein that interacts with several partner molecules including β-catenin. Here, we examined the crosstalk between EBP50 and nuclear catenin during colorectal carcinoma (CRC) progression. In clinical samples, there were no correlations between the subcellular location of EBP50 and any clinicopathological factors. However, EBP50 expression was significantly lower specifically in the outer areas of tumor lesions, in regions where tumor budding (BD) was observed. Low EBP50 expression was also significantly associated with several unfavorable prognostic factors, suggesting that EBP50 depletion rather than its overexpression or subcellular distribution plays an important role in CRC progression. In CRC cell lines, knockout of EBP50 induced epithelial-mesenchymal transition (EMT)-like features, decreased proliferation, accelerated migration capability, and stabilized nuclear β-catenin due to disruption of the interaction between EBP50 and β-catenin at the plasma membrane. In addition, Slug expression was significantly higher in outer lesions, particularly in BD areas, and was positively correlated with nuclear β-catenin status, consistent with β-catenin-driven transactivation of the Slug promoter. Together, our data suggest that EBP50 depletion releases β-catenin from the plasma membrane in outer tumor lesions, allowing β-catenin to accumulate and translocate to the nucleus, where it transactivates the Slug gene to promote EMT. This in turn triggers tumor budding and contributes to the progression of CRC to a more aggressive phase.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Cancers - 16(2023), 1 vom: 29. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Itou, Takashi [VerfasserIn] |
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| Links: |
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| Themen: |
β-catenin |
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| Anmerkungen: |
Date Revised 14.01.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/cancers16010183 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366921959 |
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Ezin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a scaffold protein that interacts with several partner molecules including β-catenin. Here, we examined the crosstalk between EBP50 and nuclear catenin during colorectal carcinoma (CRC) progression. In clinical samples, there were no correlations between the subcellular location of EBP50 and any clinicopathological factors. However, EBP50 expression was significantly lower specifically in the outer areas of tumor lesions, in regions where tumor budding (BD) was observed. Low EBP50 expression was also significantly associated with several unfavorable prognostic factors, suggesting that EBP50 depletion rather than its overexpression or subcellular distribution plays an important role in CRC progression. In CRC cell lines, knockout of EBP50 induced epithelial-mesenchymal transition (EMT)-like features, decreased proliferation, accelerated migration capability, and stabilized nuclear β-catenin due to disruption of the interaction between EBP50 and β-catenin at the plasma membrane. In addition, Slug expression was significantly higher in outer lesions, particularly in BD areas, and was positively correlated with nuclear β-catenin status, consistent with β-catenin-driven transactivation of the Slug promoter. Together, our data suggest that EBP50 depletion releases β-catenin from the plasma membrane in outer tumor lesions, allowing β-catenin to accumulate and translocate to the nucleus, where it transactivates the Slug gene to promote EMT. This in turn triggers tumor budding and contributes to the progression of CRC to a more aggressive phase | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EBP50 | |
| 650 | 4 | |a colorectal carcinoma | |
| 650 | 4 | |a tumor budding | |
| 650 | 4 | |a β-catenin | |
| 700 | 1 | |a Ishibashi, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Oguri, Yasuko |e verfasserin |4 aut | |
| 700 | 1 | |a Hashimura, Miki |e verfasserin |4 aut | |
| 700 | 1 | |a Yokoi, Ako |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 Hayashi, Misato |e verfasserin |4 aut | |
| 700 | 1 | |a Ono, Mototsugu |e verfasserin |4 aut | |
| 700 | 1 | |a Kusano, Chika |e verfasserin |4 aut | |
| 700 | 1 | |a Saegusa, Makoto |e verfasserin |4 aut | |
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