Figure 2.

Role of 27-Hydroxycholesterol in breast cancer. 27-HC is synthesized from cholesterol by CYP27A1 in the liver and other peripheral tissues. It can be further metabolized for bile acid synthesis by CYP7B1. 27-HC can be taken up by tumor cells from the circulation where it exerts ERα agonistic activity, inducing the expression of Cyclin D1 which leads to cell cycle progression and proliferation. It can also enhance the association of tumor suppressor p53 protein with MDM2 leading to its degradation. 27-HC has also been shown to promote EMT by reducing E-Cadherin and β-Catenin expression and by inducing an LXR-mediated increase in Snail and Vimentin expression. It can also activate Stat3 signaling, resulting in increased expression of MMP9 and cell invasion. 27-HC in the lungs can promote the recruitment of polymorphonuclear cells and T cells which favors the development of an immunosuppressive microenvironment that facilitates metastatic seeding and growth of breast cancer cells.