Loss of endothelial cell-specific molecule 1 promotes the tumorigenicity and metastasis of prostate cancer cells through regulation of the TIMP-1/MMP-9 expression

// Chien-Min Chen 1, 2 , Chu-Liang Lin 3 , Hui-Ling Chiou 4 , Shu-Ching Hsieh 4 , Chia-Liang Lin 3 , Chun-Wen Cheng 3 , Chia-Hung Hung 3 , Jen-Pi Tsai 5, 6 , Yi-Hsien Hsieh 3, 7, 8 1 Division of Neurosurgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan 2 School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan 4 School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan 5 School of Medicine, Tzu Chi University, Hualien, Taiwan 6 Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan 7 Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan 8 Clinical laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan Correspondence to: Jen-Pi Tsai, email: abi0918@outlook.com Yi-Hsien Hsieh, email: hyhsien@csmu.edu.tw Keywords: prostate cancer cells, endothelial cell specific molecule 1, tumorigenicity, metastasis, epithelial-mesenchymal transition Received: August 10, 2016      Accepted: January 04, 2017      Published: January 17, 2017 ABSTRACT The Endothelial cell specific molecule-1 (ESM1) protein has been involved in proliferation and metastatic progression in multiple tumors. However, there are no studies regarding the mechanism of ESM1 in prostate cancer. We found that ESM1 knockdown in prostate cancer cells resulted in increased cell proliferation and colony formation ability response evidenced by decreased expression of p21 and increased expression of cyclin D1 in prostate cancer cells. Moreover, we revealed that knockdown ESM1 also induced the epithelial-mesenchymal transition (EMT), motility and invasiveness in accordance with the upregulated the MMP-9 expression, while downregulated the TIMP-1 expression. Recombinant human (Rh) TIMP-1 significantly attenuated ESM1-mediated cell migration and invasion. Additionally, ESM1 knockdown increased in vivo tumorigenicity and metastasis of prostate cancer cells. These findings provide the first evidence that the imbalance of MMP-9/TIMP-1, is one of the regulation mechanisms by which ESM1 promotes tumorigenicity and metastasis of prostate cancer cells.