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Syndecan-2 cytoplasmic domain up-regulates matrix metalloproteinase-7 expression via the protein kinase Cγ–mediated FAK/ERK signaling pathway in colon cancer
| Content Provider | Scilit |
|---|---|
| Author | Jang, Bohee Jung, Hyejung Choi, Sojoong Lee, Young Hun Lee, Seung-Taek Oh, Eok-Soo |
| Copyright Year | 2017 |
| Description | Journal: Journal of Biological Chemistry 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 PKCγ 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 PKCγ-mediated activation of FAK/ERK signaling. |
| Related Links | http://www.jbc.org/content/292/39/16321.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625061/pdf http://www.jbc.org/article/S0021925820340187/pdf |
| Ending Page | 16332 |
| Page Count | 12 |
| Starting Page | 16321 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m117.793752 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 39 |
| Volume Number | 292 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2017-09-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Ptk2 Protein Tyrosine Kinase 2 (ptk2) (focal Adhesion Kinase) (fak) Extracellular Signal-regulated Kinase (erk) Matrix Metalloproteinase (mmp) Protein Kinase C (pkc) Receptor Protein Serine/threonine Kinase Receptor Regulation Signal Transduction |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
