Scavenger receptor class B type I r

Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development
Christiane Danilo1, Jorge L Gutierrez-Pajares1, Maria Antonietta Mainieri1, Isabelle Mercier1, Michael P Lisanti2 and Philippe G Frank13*
• *Corresponding author: Philippe G Frank Philippe.Frank@jefferson.edu
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Breast Cancer Research 2013, 15:R87 doi:10.1186/bcr3483
Published: 24 September 2013
Abstract
Introduction
Previous studies have identified cholesterol as an important regulator of breast cancer development. High-density lipoprotein (HDL) and its cellular receptor, the scavenger receptor class B type I (SR-BI) have both been implicated in the regulation of cellular cholesterol homeostasis, but their functions in cancer remain to be established.
Methods
In the present study, we have examined the role of HDL and SR-BI in the regulation of cellular signaling pathways in breast cancer cell lines and in the development of tumor in a mouse xenograft model.
Results
Our data show that HDL is capable of stimulating migration and can activate signal transduction pathways in the two human breast cancer cell lines, MDA-MB-231 and MCF7. Furthermore, we also show that knockdown of the HDL receptor, SR-BI, attenuates HDL-induced activation of the phosphatidylinositol 3-kinase (PI3K)/protein Kinase B (Akt) pathway in both cell lines. Additional investigations show that inhibition of the PI3K pathway, but not that of the mitogen-activated protein kinase (MAPK) pathway, could lead to a reduction in cellular proliferation in the absence of SR-BI. Importantly, whereas the knockdown of SR-BI led to decreased proliferation and migrationin vitro, it also led to a significant reduction in tumor growth in vivo. Most important, we also show that pharmacological inhibition of SR-BI can attenuate signaling and lead to decreased cellular proliferation in vitro. Taken together, our data indicate that both cholesteryl ester entry via HDL-SR-BI and Akt signaling play an essential role in the regulation of cellular proliferation and migration, and, eventually, tumor growth.
Conclusions
These results identify SR-BI as a potential target for the treatment of breast cancer.