27-Hydroxycholesterol induces invasion and migration of breast cancer cells by increasing MMP9 and generating EMT through activation of STAT-3.

Breast carcinoma plays a vital role in the reasons of global women's death. ER-related invasion and migration play an important part in the development and prognosis of breast cancer. Here, we found that 27-Hydroxycholesterol (27HC) could induce epithelial-mesenchymal transition (EMT) and increase the expression of the matrix metalloproteinase 9 (MMP9) at mRNA level and the active form. Meanwhile, interestingly, we found 27HC activated signal transducer and activator of transcription 3 (STAT-3) in ER positive cells except activation of ER signaling. Furthermore, inhibition of STAT-3 by siRNA attenuated the 27HC-induced improvement of MMP9 and decreased the invasion and migration ability in MCF7 and T47D cells. In addition, 27HC could also promote MMP9, vimentin and active STAT-3 in the ER negative cells MDA-MB-231. All these results not only raise a mechanism whereby 27HC enhances the invasion and metastasis, but also is helpful to realize 27HC as a potential endogenous detrimental factor in breast tumor patients.