Oncotarget

Research Papers:

Dehydropeptidase 1 promotes metastasis through regulation of E-cadherin expression in colon cancer

Sang Yoon Park, Seon-Jin Lee, Hee Jun Cho, Tae Woo Kim, Jong-Tae Kim, Jae Wha Kim, Chul-Ho Lee, Bo-Yeon Kim, Young Il Yeom, Jong-Seok Lim, Younghee Lee and Hee Gu Lee _

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Oncotarget. 2016; 7:9501-9512. https://doi.org/10.18632/oncotarget.7033

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Abstract

Sang Yoon Park1,8, Seon-Jin Lee1,2, Hee Jun Cho1, Tae Woo Kim1,2, Jong-Tae Kim1, Jae Wha Kim3, Chul-Ho Lee4, Bo-Yeon Kim5, Young Il Yeom6, Jong-Seok Lim7, Younghee Lee8, Hee Gu Lee1,2

1Genome Structure Research Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea

2Department of Biomolecular Science, University of Science and Technology (UST), Daejeon, Korea

3Biomedical Translational Research Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea

4Animal Resource Center, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea

5World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea

6Department of Functional Genomics, Korea Research Institute of Biosceience and Biotechnology, Daejeon, Korea

7Department of Biological Sciences, and The Research Center for Women’s Diseases, Sookmyung Women’s University, Seoul, Korea

8Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju, Korea

Correspondence to:

Hee Gu Lee, e-mail: hglee@kribb.re.kr

Younghee Lee, e-mail: yhl4177@chungbuk.ac.kr

Keywords: colon cancer, invasion, metastasis, E-cadherin, dehydropeptidase 1

Received: October 20, 2015    Accepted: January 19, 2016    Published: January 27, 2016

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.


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