Syndecan-2 cytoplasmic domain up-regulates matrix metalloproteinase-7 expression via the protein kinase Cγ–mediated FAK/ERK signaling pathway in colon cancer

Bohee Jang, Hyejung Jung, Sojoong Choi, Young Hun Lee, Seung Taek Lee, Eok Soo Oh

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22 Citations (Scopus)


The syndecan family of heparan sulfate proteoglycans contributes to cell adhesion and communication by serving as co-receptors for cell signaling and extracellular matrix molecules. Syndecan-2 is located at the cell surface, and we previously reported that it induces matrix metalloproteinase-7 (MMP-7) expression in colon cancer cells. However, the underlying regulatory mechanisms are unknown. Here, we report that overexpression of syndecan-2 in HT-29 colon cancer cells increases the phosphorylation of focal adhesion kinase (FAK) and ERK in parallel with up-regulated MMP-7 expression, but a syndecan-2 mutant lacking the cytoplasmic domain showed significant reductions in these effects. Consistent with this observation, FAK inhibition via FAK-related non-kinase expression or inhibition of ERK with the ERK1/2 inhibitor SCH772984 diminished the syndecan-2–mediated up-regulation of MMP-7. Activation of PKC enhanced syndecan-2–mediated MMP-7 expression, whereas inhibition of PKC had the opposite effect. Of note, the exogenous expression of syndecan-2 triggered localization of PKC to the membrane. Expression of syndecan-2 harboring a phosphomimetic (S198E) mutation of the variable region of the cytoplasmic domain enhanced MMP-7 expression and FAK phosphorylation. Finally, experimental suppression of shedding of the syndecan-2 extracellular domain did not significantly affect the syndecan-2–mediated up-regulation of MMP-7 in the early period after syndecan-2 overexpression. Taken together, these findings suggest that syndecan-2’s cytoplasmic domain up-regulates MMP-7 expression in colon cancer cells via PKC-mediated activation of FAK/ERK signaling.

Original languageEnglish
Pages (from-to)16321-16332
Number of pages12
JournalJournal of Biological Chemistry
Issue number39
Publication statusPublished - 2017 Sep 29

Bibliographical note

Funding Information:
This research was supported by National Research Foundation of Korea (NRF) Grants 2014K1A3A7A03075056 and 2016R1D1A1B03934873 funded by the Korean government (MSIP) and the Seabury Foundation. The authors declare that they have no conflicts of interest with the contents of this article.

Publisher Copyright:
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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