Bisphenol A Increases the Migration and Invasion of Triple‐Negative Breast Cancer Cells via Oestrogen‐related Receptor Gamma

Abstract

Triple-negative breast cancer (TNBC) is characterized by great metastasis and invasion capability. Our study revealed that nanomolar bisphenol A (BPA), one of the most ubiquitous endocrine disruptors, can increase wound closure and invasion of both MDA-MB-231 and BT-549 cells. BPA treatment can increase protein and mRNA expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, while had no effect on the expression of vimentin (Vim) and fibronectin (FN) in TNBC cells. The expression of G-protein-coupled receptor (GPER), which has been suggested to mediate rapid oestrogenic signals, was not varied in BPA-treated MDA-MB-231 and BT-549 cells. Its inhibitor G15 also had no effect on BPA-induced MMPs expression and cell invasion. Interestingly, BPA treatment can significantly increase the mRNA and protein expressions of oestrogen-related receptor γ (ERRγ), but not ERRα or ERRβ, in both MDA-MB-231 and BT-549 cells. The knock-down of ERRγ can markedly attenuate BPA-induced expression of MMP-2 and MMP-9 in TNBC cells. BPA treatment can activate both ERK1/2 and Akt in TNBC cells. Both inhibitors of ERK1/2 (PD98059) and Akt (LY294002) can attenuate BPA-induced ERRγ expression and cell invasion of MDA-MB-231 cells. Collectively, our data revealed that BPA can increase the expression of MMPs and in vitro motility of TNBC cells via ERRγ. Both activation of ERK1/2 and Akt participated in this process. Our study suggests that more attention should be paid to the roles of xenoestrogens such as BPA in the development and progression of TNBC.

Bisphenol A exposure promotes HTR-8/SVneo cell migration and impairs mouse placentation involving upregulation of integrin-β1 and MMP-9 and stimulation of MAPK and PI3K signaling pathways

“…We found that BPA-enhanced migration of EVT in a dose-dependent manner. BPA exposure also stimulates migration of several cancer cell lines in vitro [ 33 – 37 ]. However, these results are inconsistent with the finding that BPA inhibits the migratory and invasive abilities of HTR-8/SVneo cells at concentrations of 10 –11 M to 10 –7 M [ 16 ].…”

“…MMP-9, an autocrine factor that localizes primarily to EVT cells at 6–8 weeks of human gestation, regulates trophoblast invasion and migration by degrading ECM [ 28 , 38 , 39 ]. BPA exposure induces expression of MMP s and cell migration in several cancer cell types [ 33 , 37 ]. We confirmed that MMP-9 and MMP-2 were involved in BPA-induced EVTs migration.…”

Higher urinary bisphenol A concentration and excessive iodine intake are associated with nodular goiter and papillary thyroid carcinoma

“…Studies have shown that BPA increases estrogen-related receptor γ (ERRγ) mRNA and protein levels in breast cancer cells [45]. An inverse agonist of ERRγ, GSK5182, increases iodine uptake and enhances membrane localization of NIS in anaplastic thyroid cancer cells [46].…”

The potential for estrogen disrupting chemicals to contribute to migration, invasion and metastasis of human breast cancer cells

“…FOXA1 repression is thought to be characteristic of EMT because it is an activator of the E-cadherin gene [62] . Exposure of the human breast cancer cell lines MDA-MB-231 and BT-549 led to increased invasiveness with an associated increased expression of MMP-2 and MMP-9 [63] .…”