Bisphenol A exposure induces metastatic aggression in low metastatic MCF-7 cells via PGC-1α mediated mitochondrial biogenesis and epithelial-mesenchymal plasticity.
Life Sci
; 302: 120649, 2022 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-35597549
ABSTRACT
AIMS:
The frequency of estrogen receptor alpha (ERα)-positive breast cancers and their metastatic progression is prevalent in females globally. Aberrant interaction of estrogen-like endocrine-disrupting chemicals (EDCs) is highly implicated in breast carcinogenesis. Studies have shown that single or acute exposures of weak EDCs such as bisphenol A (BPA) may not have a substantial pro-carcinogenic/metastatic effect. However, repeated exposure to EDCs is expected to strongly induce carcinogenic/metastatic progression, which remains to be studied. MAINMETHODS:
Low metastatic ERα-positive human breast cancer cells (MCF-7) were exposed to nanomolar doses of BPA every 24 h (up to 200 days) to study the effect of repeated exposure on metastatic potential. Following the designated treatment of BPA, markers of epithelial-mesenchymal transition (EMT), migration and invasion, mitochondrial biogenesis, ATP levels, and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) knockdown assays were performed. KEYFINDINGS:
A repeated exposure of low dose BPA induced stable epithelial-mesenchymal plasticity in MCF-7 cells to augment migration and invasion in the ERα-dependent pathway. Repeated exposures of BPA increased the levels of several mesenchymal markers such as N-cadherin, vimentin, cluster of differentiation 44 (CD44), slug, and alpha-smooth muscle actin (α-SMA), whereas reduced the level of E-cadherin drastically. BPA-induced mitochondrial biogenesis favored metastatic aggression by fulfilling bioenergetics demand via PGC-1α/NRF1/ERRα signaling. Knockdown of PGC-1α resulted in suppressing both mitochondrial biogenesis and EMT in BPA exposed MCF-7 cells.SIGNIFICANCE:
Repeated exposures of low dose BPA may induce metastatic aggression in ERα-positive breast cancer cells via PGC-1α-mediated mitochondrial biogenesis and epithelial-mesenchymal plasticity.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Receptor alfa de Estrogênio
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article