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| Auteurs principaux: | , , , , , , , , , , , |
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| Format: | Artículo Open Access |
| Publié: |
Wiley
2025
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| Accès en ligne: | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6384 |
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| author | Chun‐Wei Liu Jing‐Hui Huang Hsiu‐Hao Chang Chia‐Hua Chen Yi‐Huan Tsai Wei‐Li Chen Jung‐An Lin Hsiu‐Ling Chang Cheng‐Chang Chen Mei‐Chun Lin Min‐Chuan Huang Neng‐Yu Lin |
| author_facet | Chun‐Wei Liu Jing‐Hui Huang Hsiu‐Hao Chang Chia‐Hua Chen Yi‐Huan Tsai Wei‐Li Chen Jung‐An Lin Hsiu‐Ling Chang Cheng‐Chang Chen Mei‐Chun Lin Min‐Chuan Huang Neng‐Yu Lin Chun‐Wei Liu Jing‐Hui Huang Hsiu‐Hao Chang Chia‐Hua Chen Yi‐Huan Tsai Wei‐Li Chen Jung‐An Lin Hsiu‐Ling Chang Cheng‐Chang Chen Mei‐Chun Lin Min‐Chuan Huang Neng‐Yu Lin |
| collection | Wiley Open Access |
| contents | C1GALT1 expression predicts poor survival in osteosarcoma and is crucial for ABCC1 transporter‐mediated doxorubicin resistance Chun‐Wei Liu Jing‐Hui Huang Hsiu‐Hao Chang Chia‐Hua Chen Yi‐Huan Tsai Wei‐Li Chen Jung‐An Lin Hsiu‐Ling Chang Cheng‐Chang Chen Mei‐Chun Lin Min‐Chuan Huang Neng‐Yu Lin The Journal of Pathology Abstract Osteosarcoma is an aggressive bone malignancy with a high propensity for drug resistance and metastasis, leading to poor clinical outcomes. This study investigates the role of core 1 β1,3‐galactosyltransferase 1 (C1GALT1) in osteosarcoma, focusing on its implications in chemoresistance. Our findings reveal that high expression of C1GALT1 is associated with advanced stages, adverse overall survival, and increased recurrence rates. Elevated levels of C1GALT1 were observed in doxorubicin‐selected osteosarcoma cells, where its suppression significantly promoted doxorubicin‐induced apoptosis and reduced drug efflux. Pharmacological inhibition of C1GALT1 using itraconazole replicated these effects, suggesting a potential therapeutic strategy to overcome chemoresistance. Additionally, we identified the involvement of the ATP‐binding cassette (ABC) transporter ABCC1 in the drug‐resistance phenotype mediated by C1GALT1. C1GALT1‐mediated O‐glycan changes were found to influence the cell‐surface targeting and lysosomal degradation of ABCC1, thereby modulating its efflux capacity. In vitro and in vivo studies confirmed that C1GALT1 impacts ABCC1 expression and function, further supporting its role in osteosarcoma chemoresistance. These results highlight the clinical relevance of C1GALT1 as a biomarker for prognosis and a potential therapeutic target for osteosarcoma. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6384 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/path.6384 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6384 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | C1GALT1 expression predicts poor survival in osteosarcoma and is crucial for ABCC1 transporter‐mediated doxorubicin resistance Chun‐Wei Liu Jing‐Hui Huang Hsiu‐Hao Chang Chia‐Hua Chen Yi‐Huan Tsai Wei‐Li Chen Jung‐An Lin Hsiu‐Ling Chang Cheng‐Chang Chen Mei‐Chun Lin Min‐Chuan Huang Neng‐Yu Lin The Journal of Pathology C1GALT1 expression predicts poor survival in osteosarcoma and is crucial for ABCC1 transporter‐mediated doxorubicin resistance Chun‐Wei Liu Jing‐Hui Huang Hsiu‐Hao Chang Chia‐Hua Chen Yi‐Huan Tsai Wei‐Li Chen Jung‐An Lin Hsiu‐Ling Chang Cheng‐Chang Chen Mei‐Chun Lin Min‐Chuan Huang Neng‐Yu Lin The Journal of Pathology Abstract Osteosarcoma is an aggressive bone malignancy with a high propensity for drug resistance and metastasis, leading to poor clinical outcomes. This study investigates the role of core 1 β1,3‐galactosyltransferase 1 (C1GALT1) in osteosarcoma, focusing on its implications in chemoresistance. Our findings reveal that high expression of C1GALT1 is associated with advanced stages, adverse overall survival, and increased recurrence rates. Elevated levels of C1GALT1 were observed in doxorubicin‐selected osteosarcoma cells, where its suppression significantly promoted doxorubicin‐induced apoptosis and reduced drug efflux. Pharmacological inhibition of C1GALT1 using itraconazole replicated these effects, suggesting a potential therapeutic strategy to overcome chemoresistance. Additionally, we identified the involvement of the ATP‐binding cassette (ABC) transporter ABCC1 in the drug‐resistance phenotype mediated by C1GALT1. C1GALT1‐mediated O‐glycan changes were found to influence the cell‐surface targeting and lysosomal degradation of ABCC1, thereby modulating its efflux capacity. In vitro and in vivo studies confirmed that C1GALT1 impacts ABCC1 expression and function, further supporting its role in osteosarcoma chemoresistance. These results highlight the clinical relevance of C1GALT1 as a biomarker for prognosis and a potential therapeutic target for osteosarcoma. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6384 http://creativecommons.org/licenses/by/4.0/ |
| title | C1GALT1 expression predicts poor survival in osteosarcoma and is crucial for ABCC1 transporter‐mediated doxorubicin resistance |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6384 |