Research Papers:

CCN3 promotes epithelial-mesenchymal transition in prostate cancer via FAK/Akt/HIF-1α-induced Twist expression

Po-Chun Chen, Huai-Ching Tai, Tien-Huang Lin, Shih-Wei Wang, Chih-Yang Lin, Chia-Chia Chao, Hong-Jeng Yu, Yu-Chieh Tsai, Yu-Wei Lai, Chiao-Wen Lin and Chih-Hsin Tang _

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Oncotarget. 2017; 8:74506-74518. https://doi.org/10.18632/oncotarget.20171

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Po-Chun Chen1,2,3,*, Huai-Ching Tai4,5,6,*, Tien-Huang Lin7,8, Shih-Wei Wang9, Chih-Yang Lin1, Chia-Chia Chao10, Hong-Jeng Yu4, Yu-Chieh Tsai11, Yu-Wei Lai12,13, Chiao-Wen Lin14,15 and Chih-Hsin Tang1,3,16

1Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

2Department of Medical Research, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan

3Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan

4Department of Urology, National Taiwan University Hospital, Taipei, Taiwan

5Department of Urology, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan

6School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

7Department of Urology, Buddhist Tzu Chi General Hospital Taichung Branch, Taichung, Taiwan

8School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan

9Department of Medicine, Mackay Medical College, New Taipei City, Taiwan

10Department of Respiratory Therapy, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

11Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan

12Division of Urology, Taipei City Hospital Renai Branch, Taipei, Taiwan

13Department of Urology, National Yang-Ming University School of Medicine, Taipei, Taiwan

14Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan

15Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan

16Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Chih-Hsin Tang, email: [email protected]

Chiao-Wen Lin, email: [email protected]

Keywords: CCN3, epithelial-mesenchymal transition, prostate cancer, HIF-1α

Received: May 10, 2017    Accepted: June 29, 2017    Published: August 10, 2017


Epithelial-mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm for explaining metastatic behavior during cancer progression. NOV/CCN3 is a matrix-associated protein involved in many cellular functions. Previous studies have shown that CCN3 expression is upregulated in prostate cancer (PCa) cells and in PCa patients. In this study, we have provided evidence of tumor promoting effects of CCN3, which includes induction of epithelial-to-mesenchymal transition (EMT) and tumor metastasis. We used an orthotopic in vivo model to demonstrate the prometastatic effects of CCN3. Overexpression or knockdown of CCN3 changed the EMT phenotype in PCa cells. Moreover, treatment with recombinant CCN3 promoted EMT in PCa cells. We also found that CCN3 may promote EMT by activating the FAK/Akt/HIF-1α pathway and this activation is responsible for Twist expression. IHC staining confirmed a positive correlation between the expression of CCN3, Twist, and tumor stage in PCa tissue. Our findings provide insight into the involvement of CCN3 in the EMT regulation of prostate cancer. CCN3 is a promising molecular target that may contribute to a novel therapeutic strategy against metastatic PCa.

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