CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy
Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. The clinical efficacy of vincristine (VCR) in the treatment of RB is severely limited by drug resistance. Here, we found that CD24, a GPI‐anchored protein, was overexpressed in human RB tissues and RB cell lines, and was a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-08-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12708 |
| _version_ | 1818879989999730688 |
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| author | Jie Sun Dongju Feng Huiyu Xi Jiajing Luo Zewei Zhou Qinghuai Liu Yun Chen Qing Shao |
| author_facet | Jie Sun Dongju Feng Huiyu Xi Jiajing Luo Zewei Zhou Qinghuai Liu Yun Chen Qing Shao |
| author_sort | Jie Sun |
| collection | DOAJ |
| description | Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. The clinical efficacy of vincristine (VCR) in the treatment of RB is severely limited by drug resistance. Here, we found that CD24, a GPI‐anchored protein, was overexpressed in human RB tissues and RB cell lines, and was associated with the sensitivity of RB cells in response to VCR therapy. We demonstrated that CD24 plays a critical role in impairing RB sensitivity to VCR via regulating autophagy. Mechanistically, CD24 recruits PTEN to the lipid raft domain and regulates the PTEN/AKT/mTORC1 pathway to activate autophagy. Lipid raft localization was essential for CD24 recruitment function. Collectively, our findings revealed a novel role of CD24 in regulating RB sensitivity to VCR and showed that CD24 is a potential target for improving chemotherapeutic sensitivity and RB patient outcomes. |
| first_indexed | 2024-12-19T14:38:51Z |
| format | Article |
| id | doaj.art-497c27d8a7bb4de38d6135cfa69d3396 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-19T14:38:51Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-497c27d8a7bb4de38d6135cfa69d33962022-12-21T20:17:09ZengWileyMolecular Oncology1574-78911878-02612020-08-011481740175910.1002/1878-0261.12708CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagyJie Sun0Dongju Feng1Huiyu Xi2Jiajing Luo3Zewei Zhou4Qinghuai Liu5Yun Chen6Qing Shao7Department of Ophthalmology the First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Immunology Key Laboratory of Immune Microenvironment and Disease Nanjing Medical University Nanjing ChinaDepartment of Ophthalmology the First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Immunology Key Laboratory of Immune Microenvironment and Disease Nanjing Medical University Nanjing ChinaDepartment of Immunology Key Laboratory of Immune Microenvironment and Disease Nanjing Medical University Nanjing ChinaDepartment of Ophthalmology the First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Immunology Key Laboratory of Immune Microenvironment and Disease Nanjing Medical University Nanjing ChinaDepartment of Ophthalmology the First Affiliated Hospital of Nanjing Medical University Nanjing ChinaRetinoblastoma (RB) is the most common childhood malignant intraocular tumor. The clinical efficacy of vincristine (VCR) in the treatment of RB is severely limited by drug resistance. Here, we found that CD24, a GPI‐anchored protein, was overexpressed in human RB tissues and RB cell lines, and was associated with the sensitivity of RB cells in response to VCR therapy. We demonstrated that CD24 plays a critical role in impairing RB sensitivity to VCR via regulating autophagy. Mechanistically, CD24 recruits PTEN to the lipid raft domain and regulates the PTEN/AKT/mTORC1 pathway to activate autophagy. Lipid raft localization was essential for CD24 recruitment function. Collectively, our findings revealed a novel role of CD24 in regulating RB sensitivity to VCR and showed that CD24 is a potential target for improving chemotherapeutic sensitivity and RB patient outcomes.https://doi.org/10.1002/1878-0261.12708autophagyCD24lipid raftretinoblastomavincristine |
| spellingShingle | Jie Sun Dongju Feng Huiyu Xi Jiajing Luo Zewei Zhou Qinghuai Liu Yun Chen Qing Shao CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy Molecular Oncology autophagy CD24 lipid raft retinoblastoma vincristine |
| title | CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy |
| title_full | CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy |
| title_fullStr | CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy |
| title_full_unstemmed | CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy |
| title_short | CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy |
| title_sort | cd24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy |
| topic | autophagy CD24 lipid raft retinoblastoma vincristine |
| url | https://doi.org/10.1002/1878-0261.12708 |
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