| Title: |
Chondroitin Sulfate-E Is a Negative Regulator of a Pro-Tumorigenic Wnt/Beta-Catenin-Collagen 1 Axis in Breast Cancer Cells. |
| Authors: |
Willis, Catherine M.1,2, Klüppel, Michael1,2,3 m-kluppel@northwestern.edu |
| Source: |
PLoS ONE. Aug2014, Vol. 9 Issue 8, p1-10. 10p. |
| Subject Terms: |
*CHONDROITIN sulfates, *WNT proteins, *CATENINS, *BREAST cancer, *CANCER cells, *GLYCOSAMINOGLYCANS, *PROTEIN expression |
| Abstract: |
Expression of the glycosaminoglycan chondroitin sulfate-E (CS-E) is misregulated in many human cancers, including breast cancer. Cell-surface associated CS-E has been shown to have pro-tumorigenic functions, and pharmacological treatment with exogenous CS-E has been proposed to interfere with tumor progression mediated by endogenous CS-E. However, the effects of exogenous CS-E on breast cancer cell behavior, and the molecular mechanisms deployed by CS-E are not well understood. We show here that treatment with CS-E, but not other chondroitin forms, could interfere with the invasive protrusion formation and migration of breast cancer cells in three-dimensional organotypic cultures. Microarray analysis identified transcriptional programs controlled by CS-E in these cells. Importantly, negative regulation of the pro-metastatic extracellular matrix gene Col1a1 was required for the anti-migratory effects of exogenous CS-E. Knock-down of Col1a1 gene expression mimics the effects of CS-E treatment, while exposing cells to a preformed collagen I matrix interfered with the anti-migratory effects of CS-E. In addition, CS-E specifically interfered with Wnt/beta-catenin signaling, a known pro-tumorigenic pathway. Lastly, we demonstrate that Col1a1 is a positively regulated target gene of the Wnt/beta-catenin pathway in breast cancer cells. Together, our data identify treatment with exogenous CS-E as negative regulatory mechanism of breast cancer cell motility through interference with a pro-tumorigenic Wnt/beta-catenin - Collagen I axis. [ABSTRACT FROM AUTHOR] |
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| Database: |
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