Dehydropeptidase 1 promotes metastasis through regulation of E-cadherin expression in colon canceropen access
- Authors
- Park, Sang Yoon; Lee, Seon-Jin; Cho, Hee Jun; Kim, Tae Woo; Kim, Jong-Tae; Kim, Jae Wha; Lee, Chul-Ho; Kim, Bo-Yeon; Yeom, Young Il; Lim, Jong-Seok; Lee, Younghee; Lee, Hee Gu
- Issue Date
- Feb-2016
- Publisher
- IMPACT JOURNALS LLC
- Keywords
- colon cancer; invasion; metastasis; E-cadherin; dehydropeptidase 1
- Citation
- ONCOTARGET, v.7, no.8, pp 9501 - 9512
- Pages
- 12
- Journal Title
- ONCOTARGET
- Volume
- 7
- Number
- 8
- Start Page
- 9501
- End Page
- 9512
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/3561
- DOI
- 10.18632/oncotarget.7033
- ISSN
- 1949-2553
1949-2553
- 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-beta-induced EMT. TGF-beta transcriptionally repressed DPEP1 expression. TGF-beta 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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