Abstract
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.
Original language | English (US) |
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Pages (from-to) | 724-733 |
Number of pages | 10 |
Journal | Journal of Lipid Research |
Volume | 47 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2006 |
Keywords
- Bile acids
- Deoxycholate
- Farnesoid X receptor
- Urokinase-type plasminogen activator
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology