title: 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.
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.
authors.affiliation: Division of Neurosurgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.|School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Min
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chu-Liang
authors.initials: CL
authors.lastname: Lin
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chiou
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Hsieh
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chia-Liang
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Hung
authors.affiliation: School of Medicine, Tzu Chi University, Hualien, Taiwan.|Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
authors.forename: Jen-Pi
authors.initials: JP
authors.lastname: Tsai
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.|Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Clinical laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*
chemical_list: C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: endothelial cell specific molecule 1; epithelial-mesenchymal transition; metastasis; prostate cancer cells; tumorigenicity