Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells.
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.
Department of Life Sciences and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 03760, Republic of Korea.
Bohee
B
Jang
Department of Life Sciences and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 03760, Republic of Korea.
Hyejung
H
Jung
Department of Life Sciences and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 03760, Republic of Korea.
Heesung
H
Chung
Department of Surgery, College of Medicine, Ewha Womans University, 911-1 Mok-Dong Yangcheon-Ku, Seoul, 158-710, Republic of Korea. Electronic address: mbit@ewha.ac.kr.
Byung-In
BI
Moon
Department of Life Sciences and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 03760, Republic of Korea. Electronic address: OhES@ewha.ac.kr.
Eok-Soo
ES
Oh
D015820:Cadherins / Q000378:metabolism*; D003110:Colonic Neoplasms; D019073:HT29 Cells; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D053669:Syndecan-2 / Q000378:metabolism*
D015820:Cadherins; D053669:Syndecan-2; D020783:Matrix Metalloproteinase 7
Colon cancer; E-cadherin; E-cadherin shedding; Epithelial mesenchymal transition; Matrix metalloprotease-7; Syndecan-2