title: Dehydropeptidase 1 promotes metastasis through regulation of E-cadherin expression in colon cancer.
abstract: Dehydropeptidase 1 (DPEP1) is a zinc-dependent metalloproteinase that is expressed aberrantly in several cancers. The role of DPEP1 in cancer remain controversial. In this study, we demonstrate that DPEP1 functions as a positive regulator for colon cancer cell metastasis. The expression of DPEP1 mRNA and proteins were upregulated in colon cancer tissues compared to normal mucosa. Gain-of-function and loss-of-function approaches were used to examine the malignant phenotype of DPEP1-expressing or DPEP1-depleted cells. DPEP1 expression caused a significant increase in colon cancer cell adhesion and invasion in vitro, and metastasis in vivo. In contrast, DPEP1 depletion induced opposite effects. Furthermore, cilastatin, a DPEP1 inhibitor, suppressed the invasion and metastasis of DPEP1-expressing cells. DPEP1 inhibited the leukotriene D4 signaling pathway and increased the expression of E-cadherin. We also show that DPEP1 mediates TGF-β-induced EMT. TGF-β transcriptionally repressed DPEP1 expression. TGF-β treatment decreased E-cadherin expression and promoted cell invasion in DPEP1-expressing colon cancer cell lines, whereas it did not affect these parameters in DPEP1-depleted cell lines. These results suggest that DPEP1 promotes cancer metastasis by regulating E-cadherin plasticity and that it might be a potential therapeutic target for preventing the progression of colon cancer.
authors.affiliation: Genome Structure Research Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea.|Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju, Korea.
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Genome Structure Research Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea.|Department of Biomolecular Science, University of Science and Technology (UST), Daejeon, Korea.
authors.forename: Seon-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Genome Structure Research Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea.
authors.forename: Hee Jun
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Genome Structure Research Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea.|Department of Biomolecular Science, University of Science and Technology (UST), Daejeon, Korea.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Genome Structure Research Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea.
authors.forename: Jong-Tae
authors.initials: JT
authors.lastname: Kim
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea.
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Animal Resource Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
authors.affiliation: World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea.
authors.forename: Bo-Yeon
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Department of Functional Genomics, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yeom
authors.affiliation: Department of Biological Sciences, and The Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju, Korea.
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Genome Structure Research Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea.|Department of Biomolecular Science, University of Science and Technology (UST), Daejeon, Korea.
authors.forename: Hee Gu
authors.initials: HG
authors.lastname: Lee
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D015377:Cilastatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D004150:Dipeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D058851:GPI-Linked Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D015377:Cilastatin; D017998:Leukotriene D4; D004150:Dipeptidases; C549872:dipeptidase 1
keywords: E-cadherin; colon cancer; dehydropeptidase 1; invasion; metastasis
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