Research Papers:

Endothelin-1 promotes epithelial–mesenchymal transition in human chondrosarcoma cells by repressing miR-300

Min-Huan Wu _, Pei-Han Huang, Mingli Hsieh, Chun-Hao Tsai, Hsien-Te Chen and Chih-Hsin Tang

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Oncotarget. 2016; 7:70232-70246. https://doi.org/10.18632/oncotarget.11835

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Min-Huan Wu1,2, Pei-Han Huang3, Mingli Hsieh4, Chun-Hao Tsai5,6, Hsien-Te Chen5,7, Chih-Hsin Tang3,6,8

1Physical Education Office, Tunghai University, Taichung, Taiwan

2Sports Recreation and Health Management Continuing Studies, Tunghai University, Taichung, Taiwan

3Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

4Department of Life Science, Tunghai University, Taichung, Taiwan

5Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan

6School of Medicine, China Medical University, Taichung, Taiwan

7School of Chinese Medicine, China Medical University, Taichung, Taiwan

8Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan

Correspondence to:

Chih-Hsin Tang, email: [email protected]

Keywords: Endothelin-1, epithelial to mesenchymal transition, AMPK, Twist, miR-300

Received: June 16, 2016    Accepted: August 26, 2016    Published: September 02, 2016


Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis. We report that ET-1 promotes epithelial–mesenchymal transition (EMT) in human chondrosarcoma cells. EMT is a key pathological event in cancer progression, during which epithelial cells lose their junctions and apical-basal polarity and adopt an invasive phenotype. Our study verifies that ET-1 induces the EMT phenotype in chondrosarcoma cells via the AMP-activated protein kinase (AMPK) pathway. In addition, we show that ET-1 increases EMT by repressing miR-300, which plays an important role in EMT-enhanced tumor metastasis. We also show that miR-300 directly targets Twist, which in turn results in a negative regulation of EMT. We found a highly positive correlation between ET-1 and Twist expression levels as well as tumor stage in chondrosarcoma patient specimens. Therefore, ET-1 may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis.

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