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EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression

Chondrosarcomas 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 dedifferentiated subtype. At present, the surgical resection of chondro...

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Autores principales: Lin, Zong-Shin, Chung, Chiao-Chen, Liu, Yu-Chia, Chang, Chu-Han, Liu, Hui-Chia, Liang, Yung-Yi, Huang, Teng-Le, Chen, Tsung-Ming, Lee, Che-Hsin, Tang, Chih-Hsin, Hung, Mien-Chie, Chen, Ya-Huey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829410/
https://www.ncbi.nlm.nih.gov/pubmed/36622753
http://dx.doi.org/10.7554/eLife.79432
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author Lin, Zong-Shin
Chung, Chiao-Chen
Liu, Yu-Chia
Chang, Chu-Han
Liu, Hui-Chia
Liang, Yung-Yi
Huang, Teng-Le
Chen, Tsung-Ming
Lee, Che-Hsin
Tang, Chih-Hsin
Hung, Mien-Chie
Chen, Ya-Huey
author_facet Lin, Zong-Shin
Chung, Chiao-Chen
Liu, Yu-Chia
Chang, Chu-Han
Liu, Hui-Chia
Liang, Yung-Yi
Huang, Teng-Le
Chen, Tsung-Ming
Lee, Che-Hsin
Tang, Chih-Hsin
Hung, Mien-Chie
Chen, Ya-Huey
author_sort Lin, Zong-Shin
collection PubMed
description Chondrosarcomas 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 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. Here, we identify a signal pathway way involving EZH2/SULF1/cMET axis that contributes to malignancy of chondrosarcoma and provides a potential therapeutic option for the disease. A non-biased chromatin immunoprecipitation sequence, cDNA microarray analysis, and validation of chondrosarcoma cell lines identified sulfatase 1 (SULF1) as the top EZH2-targeted gene to regulate chondrosarcoma progression. Overexpressed EZH2 resulted in downregulation of SULF1 in chondrosarcoma cell lines, which in turn activated cMET pathway. Pharmaceutical inhibition of cMET or genetically silenced cMET pathway significantly retards the chondrosarcoma growth and extends mice survival. The regulation of EZH2/SULF1/cMET axis were further validated in patient samples with chondrosarcoma. The results not only established a signal pathway promoting malignancy of chondrosarcoma but also provided a therapeutic potential for further development of effective target therapy to treat chondrosarcoma.
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spelling pubmed-98294102023-01-10 EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression Lin, Zong-Shin Chung, Chiao-Chen Liu, Yu-Chia Chang, Chu-Han Liu, Hui-Chia Liang, Yung-Yi Huang, Teng-Le Chen, Tsung-Ming Lee, Che-Hsin Tang, Chih-Hsin Hung, Mien-Chie Chen, Ya-Huey eLife Cancer Biology Chondrosarcomas 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 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. Here, we identify a signal pathway way involving EZH2/SULF1/cMET axis that contributes to malignancy of chondrosarcoma and provides a potential therapeutic option for the disease. A non-biased chromatin immunoprecipitation sequence, cDNA microarray analysis, and validation of chondrosarcoma cell lines identified sulfatase 1 (SULF1) as the top EZH2-targeted gene to regulate chondrosarcoma progression. Overexpressed EZH2 resulted in downregulation of SULF1 in chondrosarcoma cell lines, which in turn activated cMET pathway. Pharmaceutical inhibition of cMET or genetically silenced cMET pathway significantly retards the chondrosarcoma growth and extends mice survival. The regulation of EZH2/SULF1/cMET axis were further validated in patient samples with chondrosarcoma. The results not only established a signal pathway promoting malignancy of chondrosarcoma but also provided a therapeutic potential for further development of effective target therapy to treat chondrosarcoma. eLife Sciences Publications, Ltd 2023-01-09 /pmc/articles/PMC9829410/ /pubmed/36622753 http://dx.doi.org/10.7554/eLife.79432 Text en © 2023, Lin et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Lin, Zong-Shin
Chung, Chiao-Chen
Liu, Yu-Chia
Chang, Chu-Han
Liu, Hui-Chia
Liang, Yung-Yi
Huang, Teng-Le
Chen, Tsung-Ming
Lee, Che-Hsin
Tang, Chih-Hsin
Hung, Mien-Chie
Chen, Ya-Huey
EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression
title EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression
title_full EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression
title_fullStr EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression
title_full_unstemmed EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression
title_short EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression
title_sort ezh2/hsulf1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829410/
https://www.ncbi.nlm.nih.gov/pubmed/36622753
http://dx.doi.org/10.7554/eLife.79432
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