KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axis
Abstract Chondrosarcoma (CS) is the second most common primary bone malignancy, known for its unique transcriptional landscape that renders most CS subtypes resistant to chemotherapy, including neoadjuvant chemotherapy commonly used in osteosarcoma (OS) treatment. Understanding the transcriptional l...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-024-07264-7 |
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| _version_ | 1846100866631729152 |
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| author | Huabin Yin Dongjie Jiang Yongai Li Wenjun Chen Jie Zhang Xinghai Yang Jinbo Hu Haifeng Wei |
| author_facet | Huabin Yin Dongjie Jiang Yongai Li Wenjun Chen Jie Zhang Xinghai Yang Jinbo Hu Haifeng Wei |
| author_sort | Huabin Yin |
| collection | DOAJ |
| description | Abstract Chondrosarcoma (CS) is the second most common primary bone malignancy, known for its unique transcriptional landscape that renders most CS subtypes resistant to chemotherapy, including neoadjuvant chemotherapy commonly used in osteosarcoma (OS) treatment. Understanding the transcriptional landscape of CS and the mechanisms by which key genes contribute to chemotherapy resistance could be a crucial step in overcoming this challenge. To address this, we developed a single-cell transcriptional map of CS, comparing it with OS and normal cancellous bone. Our analysis revealed a specific increase in KDEL receptor 1 (KDELR1) expression in CS, which was closely associated with CS prognosis, tumor aggressiveness, and drug resistance. KDELR1 plays a key role in regulating membrane protein processing and secretion, as well as contributing to tumor extracellular matrix (ECM) formation and drug resistance. Further investigation using mass spectrometry proteomics and transcriptomics uncovered KDELR1’s involvement in modulating the Hippo-YAP pathway activity in CS cells. The KDELR1-Integrin-PLCγ-YAP1 axis emerges as a critical process mediating drug resistance and malignant behavior in CS, offering novel insights and potential therapeutic targets for CS treatment. |
| format | Article |
| id | doaj-art-ea44786afff24fe282b6ad35c83c8dbf |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-ea44786afff24fe282b6ad35c83c8dbf2024-12-29T12:49:47ZengNature Publishing GroupCell Death and Disease2041-48892024-12-01151211210.1038/s41419-024-07264-7KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axisHuabin Yin0Dongjie Jiang1Yongai Li2Wenjun Chen3Jie Zhang4Xinghai Yang5Jinbo Hu6Haifeng Wei7Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineSpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical UniversityDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineSpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical UniversitySpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical UniversitySpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical UniversitySpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical UniversitySpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical UniversityAbstract Chondrosarcoma (CS) is the second most common primary bone malignancy, known for its unique transcriptional landscape that renders most CS subtypes resistant to chemotherapy, including neoadjuvant chemotherapy commonly used in osteosarcoma (OS) treatment. Understanding the transcriptional landscape of CS and the mechanisms by which key genes contribute to chemotherapy resistance could be a crucial step in overcoming this challenge. To address this, we developed a single-cell transcriptional map of CS, comparing it with OS and normal cancellous bone. Our analysis revealed a specific increase in KDEL receptor 1 (KDELR1) expression in CS, which was closely associated with CS prognosis, tumor aggressiveness, and drug resistance. KDELR1 plays a key role in regulating membrane protein processing and secretion, as well as contributing to tumor extracellular matrix (ECM) formation and drug resistance. Further investigation using mass spectrometry proteomics and transcriptomics uncovered KDELR1’s involvement in modulating the Hippo-YAP pathway activity in CS cells. The KDELR1-Integrin-PLCγ-YAP1 axis emerges as a critical process mediating drug resistance and malignant behavior in CS, offering novel insights and potential therapeutic targets for CS treatment.https://doi.org/10.1038/s41419-024-07264-7 |
| spellingShingle | Huabin Yin Dongjie Jiang Yongai Li Wenjun Chen Jie Zhang Xinghai Yang Jinbo Hu Haifeng Wei KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axis Cell Death and Disease |
| title | KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axis |
| title_full | KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axis |
| title_fullStr | KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axis |
| title_full_unstemmed | KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axis |
| title_short | KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axis |
| title_sort | kdelr1 regulates chondrosarcoma drug resistance and malignant behavior through intergrin hippo yap1 axis |
| url | https://doi.org/10.1038/s41419-024-07264-7 |
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