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

Environ Toxicol Pharmacol. 2017 Apr:51:1-8. doi: 10.1016/j.etap.2017.02.001. Epub 2017 Feb 10.

Abstract

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.

Keywords: 27-Hydroxycholesterol; Breast cancer; Epithelial-mesenchymal transition; Invasion and migration; Matrix metalloproteinase 9; Signal transducer and activator of transcription 3.

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Culture Techniques
  • Cell Movement / drug effects*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Hydroxycholesterols / metabolism
  • Hydroxycholesterols / toxicity*
  • MCF-7 Cells
  • Matrix Metalloproteinase 9 / metabolism*
  • Neoplasm Invasiveness
  • Real-Time Polymerase Chain Reaction
  • Receptors, Estrogen / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / metabolism*
  • Transfection

Substances

  • Hydroxycholesterols
  • Receptors, Estrogen
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • 27-hydroxycholesterol
  • MMP9 protein, human
  • Matrix Metalloproteinase 9