Promoter hypermethylation of membrane type 3 matrix metalloproteinase is associated with cell migration in colorectal adenocarcinoma

Ji Wook Moon, Jong Ho Choi, Soo Kyung Lee, Yong Woo Lee, Jung Ok Lee, Nami Kim, Hye Jeong Lee, Jung Seon Seo, Jin Kim, Hyeon Soo Kim, Gi Jin Kim, Sun-Hwa Park

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The gene MT3-MMP (also known as MMP16) encodes the membrane type 3 matrix metalloproteinase, which is a member of the matrix metalloproteinase (. MMP) gene family. Several MMPs are associated with migration in colorectal cancer (CRC). However, the methylation status of the MT3-MMP promoter in CRC has not been reported. The methylation status and expression levels of MT3-MMP were investigated in primary tumor tissues and adjacent normal tissues in 105 patients with CRC, one normal colon cell line (CCD18Co), and three CRC cell lines (SW480, DLD-1, and LoVo) by quantitative methylation-specific PCR and real-time PCR. MT3-MMP was hypermethylated in 82 of 105 CRC tissues (78%), 30 of 105 adjacent normal tissues (29%), and two of 11 normal colon tissues (18%). MT3-MMP mRNA was significantly reduced in CRC compared with that in adjacent normal tissues (. P<0.05). The methylation-mediated downregulation of MT3-MMP was restored by treatment with 5-aza-2'-deoxycytidine in two CRC cell lines, and MT3-MMP promoter activity was significantly reduced by methylation. The knockdown of MT3-MMP induced cell migration, but overexpressed MT3-MMP reduced cell migration in CRC cells. These results demonstrate that the MT3-MMP promoter is frequently hypermethylated in CRC and that downregulation of MT3-MMP may be important for cell migration in CRC.

Original languageEnglish
Pages (from-to)261-270
Number of pages10
JournalCancer genetics
Volume208
Issue number5
DOIs
Publication statusPublished - 2015 May 1

Keywords

  • Colorectal cancer
  • Hypermethylation
  • Migration
  • MMP16
  • MT3-MMP

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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