Hyaluronan Synthase 2 (HAS2) Promotes Breast Cancer Cell Invasion by Suppression of Tissue Metalloproteinase Inhibitor 1 (TIMP-1)
| Autor: | Berit Bernert, Paraskevi Heldin, Helena Porsch |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
endocrine system
Metalloproteinase Inhibitor 1 Glycobiology and Extracellular Matrices Apoptosis Breast Neoplasms Biology Hyaluronan Synthase 2 Biochemistry Gene Expression Regulation Enzymologic Metastasis Focal adhesion Breast cancer Cell Line Tumor medicine Humans Neoplasm Invasiveness Glucuronosyltransferase Neoplasm Metastasis Phosphorylation RNA Small Interfering Molecular Biology PI3K/AKT/mTOR pathway Tissue Inhibitor of Metalloproteinase-1 Akt/PKB signaling pathway Glycosyltransferases Cell Biology medicine.disease Hyaluronan-mediated motility receptor Gene Expression Regulation Neoplastic Cancer research Female Hyaluronan Synthases Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 286:42349-42359 |
| ISSN: | 0021-9258 |
| Popis: | Invasion and metastasis are the primary causes of breast cancer mortality, and increased knowledge about the molecular mechanisms involved in these processes is highly desirable. High levels of hyaluronan in breast tumors have been correlated with poor patient survival. The involvement of hyaluronan in the early invasive phase of a clone of breast cancer cell line MDA-MB-231 that forms bone metastases was studied using an in vivo-like basement membrane model. The metastatic to bone tumor cells exhibited a 7-fold higher hyaluronan-synthesizing capacity compared with MDA-MB-231 cells predominately due to an increased expression of hyaluronan synthase 2 (HAS2). We found that knockdown of HAS2 completely suppressed the invasive capability of these cells by the induction of tissue metalloproteinase inhibitor 1 (TIMP-1) and dephosphorylation of focal adhesion kinase. HAS2 knockdown-mediated inhibition of basement membrane remodeling was rescued by HAS2 overexpression, transfection with TIMP-1 siRNA, or addition of TIMP-1-blocking antibodies. Moreover, knockdown of HAS2 suppressed the EGF-mediated induction of the focal adhesion kinase/PI3K/Akt signaling pathway. Thus, this study provides new insights into a possible mechanism whereby HAS2 enhances breast cancer invasion. |
| Databáze: | OpenAIRE |
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