EZH2/ hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression
EZH2/ hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression
Abstract BackgroundChondrosarcomas are primary cancers of cartilaginous tissue and capable of alteration to highly aggressive, metastatic, and treatment-refractory states, leading to a poor prognosis with a five-year survival rate at 11 months for the dedifferentiated subtype. At present, the surgical resection of chondrosarcoma is the only effective treatment, and no other treatment options including targeted therapies, conventional chemotherapies, or immunotherapies are available for these patients. MethodsA non-biased ChIP sequence, cDNA microarray analysis, and validation of chondrosarcoma cell lines identified sulfatase 1(SULF1) as the top EZH2-targeted gene to regulate chondrosarcoma progression. Receptor tyrosine kinase (RTK) array of chondrosarcoma cells with vector control or ectopically expressed SULF1 revealed that cMET was the downstream signal. The regulation of the EZH2/SULF1/cMET axis was further validated in mice and patient samples with mice models and chondrosarcoma tissue array, respectively. ResultsThe EZH2/SULF1/cMET axis is identified, which contributes to the malignancy of chondrosarcoma and provides a potential therapeutic option for the disease. Ectopically expressed SULF1 or pharmaceutical inhibition of the cMET pathway significantly retards the chondrosarcoma growth and extends mice survival. ConclusionsThe results not only established a signal pathway promoting the malignancy of chondrosarcoma but also provided a therapeutic potential for further development of effective target therapy to treat chondrosarcoma.
Chung Chiao-Chen、Liang Yung-Yi、Huang Teng-Le、Chen Tsung-Ming、Tang Chih-Hsin、Lee Che-Hsin、Chen Ya-Huey、Hung Mien-Chie、Liu Hui-Chia、Chang Chu-Han、Liu Yu-Chia、Lin Zong-Shin
Center for Molecular Medicine, China Medical University Hospital TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical UniversityDepartment of Biomedical Imaging and Radiological Science, College of Medicine, China Medical UniversityDepartment and Graduate Institute of Aquaculture, National Kaohsiung Marine UniversityGraduate Institute of Biomedical Sciences, College of Medicine, China Medical UniversityDepartment of Biological Sciences, National Sun Yat-sen UniversityGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University||Center for Molecular Medicine, China Medical University Hospital TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University||Center for Molecular Medicine, China Medical University Hospital Taiwan||Department of Biotechnology, Asia UniversityCenter for Molecular Medicine, China Medical University Hospital TaiwanCenter for Molecular Medicine, China Medical University Hospital TaiwanCenter for Molecular Medicine, China Medical University Hospital TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University
肿瘤学基础医学分子生物学
Chung Chiao-Chen,Liang Yung-Yi,Huang Teng-Le,Chen Tsung-Ming,Tang Chih-Hsin,Lee Che-Hsin,Chen Ya-Huey,Hung Mien-Chie,Liu Hui-Chia,Chang Chu-Han,Liu Yu-Chia,Lin Zong-Shin.EZH2/ hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression[EB/OL].(2025-03-28)[2025-05-21].https://www.biorxiv.org/content/10.1101/2022.06.07.495151.点此复制
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