Journal
JOURNAL OF LIPID RESEARCH
Volume 47, Issue 4, Pages 724-733Publisher
ELSEVIER
DOI: 10.1194/jlr.M500473-JLR200
Keywords
bile acids; deoxycholate; farnesoid X receptor; urokinase-type plasminogen activator
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Bone is the most common site to which breast cancer cells metastasize. We found that osteoblast-like MG63 cells and human bone tissue contain the bile acid salt sodium deoxycholate ( DC). MG63 cells take up and accumulate DC from the medium, suggesting that the bone-derived DC originates from serum. DC released from MG63 cells or bone tissue promotes cell survival and induces the migration of metastatic human breast cancer MDA-MB-231 cells. The bile acid receptor farnesoid X receptor (FXR) antagonist Z-guggulsterone prevents the migration of these cells and induces apoptosis. DC increases the gene expression of FXR and induces its translocation to the nucleus of MDA-MB-231 cells. Nuclear translocation of FXR is concurrent with the increase of urokinase-type plasminogen activator (uPA) and the formation of F-actin, two factors critical for the migration of breast cancer cells. Our results suggest a novel mechanism by which DC-induced increase of uPA and binding to the uPA receptor of the same breast cancer cell self-propel its migration and metastasis to the bone. - Silva, J., S. Dasgupta, G. Wang, K. Krishnamurthy, E. Ritter, and E. Bieberich. Lipids isolated from bone induce the migration of human breast cancer cells.
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