Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells

Bohee Jang, Hyejung Jung, Heesung Chung, Byung In Moon, Eok Soo Oh

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

E-cadherin plays a mechanical role in mediating cell-cell interactions and maintaining epithelial tissue integrity, and the loss of E-cadherin function has been implicated in cancer progression and metastasis. Syndecan-2, a cell-surface heparan sulfate proteoglycan, is upregulated during the development of colon cancer. Here, we assessed the functional relationship between E-cadherin and syndecan-2. We found that stable overexpression of syndecan-2 in a human colorectal adenocarcinoma cell line (HT29) enhanced the proteolytic shedding of E-cadherin to conditioned-media. Either knockdown of matrix metalloproteinase 7 (MMP-7) or inhibition of MMP-7 activity using GM6001 significantly reduced the extracellular shedding of E-cadherin, suggesting that syndecan-2 mediates E-cadherin shedding via MMP-7. Consistent with this notion, enhancement of MMP-7 expression by interleukin-1α treatment increased the shedding of E-cadherin. Conversely, the specific reduction of either syndecan-2 or MMP-7 reduced the shedding of E-cadherin. HT29 cells overexpressing syndecan-2 showed significantly lower cell-surface expression of E-cadherin, decreased cell-cell contact, a more fibroblastic cell morphology, and increased expression levels of ZEB-1. Taken together, these data suggest that syndecan-2 induces extracellular shedding of E-cadherin and supports the acquisition of a fibroblast-like morphology by regulating MMP-7 expression in a colon cancer cell line.

Original languageEnglish
Pages (from-to)47-53
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume477
Issue number1
DOIs
StatePublished - 12 Aug 2016

Keywords

  • Colon cancer
  • E-cadherin
  • E-cadherin shedding
  • Epithelial mesenchymal transition
  • Matrix metalloprotease-7
  • Syndecan-2

Fingerprint

Dive into the research topics of 'Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells'. Together they form a unique fingerprint.

Cite this