SOX2
癌症研究
粒体自噬
卵巢癌
癌症干细胞
癌症
同源盒蛋白纳米
转移
生物
化学
内科学
医学
细胞凋亡
生物化学
转录因子
自噬
胚胎干细胞
诱导多能干细胞
基因
作者
Xiaoyu Yuan,Kelie Chen,Fang Zheng,Sinan Xu,Yating Li,Yuwei Wang,Heng Ni,Sheng Wang,Zhenyan Cui,Yuheng Qin,Dajing Xia,Yihua Wu
标识
DOI:10.1016/j.jhazmat.2023.131288
摘要
The environmental toxicity of bisphenol A (BPA) and its analog like bisphenol S (BPS) have drawn wide attention, but their roles in cancer progression remain controversial. Here, we investigated the effect of BPA/BPS on the development of ovarian cancer. Human internal BPA/BPS exposure levels were analyzed from NHANES 2013–2016 data. We treated human ovarian cancer cells with 0−1000 nM BPA/BPS and found that 100 nM BPA/BPS treatment significantly increased Cancer Stem Cell (CSC) markers expression including OCT4, NANOG and SOX2. Cancer cell stemness evaluation induced by BPA/BPS was notably attenuated by the knockdown of PINK1 or Mdivi-1 treatment. The activation of PINK1 initiated mitophagy by inhibiting p-p53 nuclear translocation in a non-canonical manner. In vivo studies validated that BPA/BPS-exposed mice have higher tumor metastasis incidence compared with the control group, while mitophagy inhibition blocked such a promotion effect. In addition, CSC markers such as SOX2 had been found to be overexpressed in the tumor tissues of BPA/BPS exposure group. Taken together, the findings herein first provide the evidence that environmentally relevant BPA/BPS exposure could enhance ovarian cancer cell stemness through a non-canonical PINK1/p53 mitophagic pathway, raising concerns about the potential population hazards of BPA and other bisphenol analogs.
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