Suppression of ferroportin expression by cadmium stimulates proliferation, EMT, and migration in triple-negative breast cancer cells.
Suppression of ferroportin expression by cadmium stimulates proliferation, EMT, and migration in triple-negative breast cancer cells.
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DOI：
10.1016/j.taap.2018.07.017
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发表时间：
2018-10-01
影响因子：
3.8
通讯作者：
Shaikh ZA
中科院分区：
文献类型：
--
作者：
Shan Z;Wei Z;Shaikh ZA
镉（Cd）与多种癌症有关，包括乳腺癌；然而，其致癌活性的分子机制尚不完全清楚。为此，本研究调查了铁转运蛋白（FPN），乳腺癌的预后标志物，在cd诱导的细胞增殖和细胞迁移的刺激中的作用。三阴性MDA-MB-231细胞经1-3 μM Cd处理后，细胞中FPN表达显著降低，铁浓度随之升高。Cd处理8周后，细胞增殖和迁移活性升高，与FPN表达呈负相关。E-cadherin表达增加，N-cadherin、Twist和Slug表达减少，表明FPN表达减少也导致EMT。进一步的研究表明，Cd至少部分通过激活TGF-ß抑制FPN表达，TGF-ß是一种已知的FPN表达调节因子。综上所述，这些结果表明cd诱导的MDA-MB-231细胞增殖、EMT和迁移的刺激是通过抑制FPN表达和相关的铁稳态破坏来实现的。
Cadmium (Cd) has been linked to a variety of cancers, including breast cancer; however, the molecular mechanism of its carcinogenic activity is not fully understood. To this end, the present study investigated the roles of ferroportin (FPN), a prognostic marker of breast cancer, in Cd-induced stimulation of cell proliferation and cell migration. Triple-negative MDA-MB-231 cells were treated with 1–3 μM Cd. The cells exhibited significant reduction in FPN expression and concomitant increase in iron concentration. Cells treated with Cd for 8 weeks displayed elevated proliferative and migratory activities which were inversely related with FPN expression. Reduced FPN expression also resulted in EMT as indicated by an increase in the expression of E-cadherin, and a decrease in the expression of N-cadherin, Twist and Slug. Further investigation revealed that Cd suppressed FPN expression at least partially by activating TGF-ß, a known regulator of FPN expression. Taken together, these results indicate that Cd-induced stimulation of MDA-MB-231 cell proliferation, EMT, and migration is brought about by suppression of FPN expression and associated disruption of iron homeostasis.
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影响因子：
5.6
作者：
Asara Y;Marchal JA;Carrasco E;Boulaiz H;Solinas G;Bandiera P;Garcia MA;Farace C;Montella A;Madeddu R
通讯作者：
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影响因子：
6.2
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影响因子：
3.8
作者：
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影响因子：
11.1
作者：
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通讯作者：
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