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Title 

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

Authors 

Sang Yoon ParkSeon-Jin LeeHee Jun ChoTae Woo KimJong Tae KimJae Wha KimChul Ho LeeBo Yeon KimYoung Il YeomJ S LimY LeeHee Gu Lee

Publisher 

Impact Journals

Issue Date 

2016

Citation 

Oncotarget, vol. 7, no. 8, pp. 9501-9512

Keywords 

Colon cancerDehydropeptidase 1E-cadherinInvasionMetastasis

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. Gainof- 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.

ISSN 

1949-2553

Link 

http://dx.doi.org/10.18632/oncotarget.7033

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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