HRG-β1-driven ErbB3 signaling induces epithelial-mesenchymal transition in breast cancer cells.
HRG-β1-driven ErbB3 signaling induces epithelial-mesenchymal transition in breast cancer cells.
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DOI：
10.1186/1471-2407-13-383
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发表时间：
2013-08-12
期刊：
影响因子：
3.8
通讯作者：
Kim A
中科院分区：
文献类型：
--
作者：
Kim J;Jeong H;Lee Y;Kim C;Kim H;Kim A
Hereglin(HRG；也称为neuRegin)是ErbB3的配体。其同型之一HrG-β1与ErbB3结合，与ErbB家族其他成员形成异二聚体，从而促进乳腺癌细胞增殖和肿瘤发生。HRG刺激可能参与了乳腺癌上皮-间充质转化(EMT)和肿瘤转移的进程。大多数关于转化生长因子-β信号转导通路的研究都集中在转化生长因子-DNA信号转导方面。因此，我们研究了HRG-β1和ErbB3在乳腺癌细胞EMT过程中是否激活了Smad2信号通路。以SK-BR-3和MCF7乳腺癌细胞株为研究对象。用Western blotting和免疫荧光方法检测hrg-β-1作用后细胞中磷酸化Smad2和EMT标志物的表达。通过伤口愈合和基质侵袭实验检测细胞的运动和侵袭能力。用Smad2和ErbB3小干扰RNA(SiRNA)检测ErbB3和Smad2在HRG-β1诱导的子宫内膜转化中的作用。HRG-β1通过激活Smad2诱导EMT。HRG-β-1治疗后E-钙粘蛋白表达降低，Snail、波形蛋白和纤维连接蛋白表达增加。PI3K抑制剂LY294002或两种磷酸化Smad2抑制剂PD169316或SB203580可抑制hrg-β1诱导的蜗牛、波形蛋白和纤维连接蛋白的表达，并抑制hrg-β1诱导的癌细胞迁移。Smad2基因的下调抑制了hrg-β1刺激后Snail和FN的表达，而ErbB3基因的下调抑制了hRG-β1诱导的磷酸化Smad2、Snail和FN的表达，而E-钙粘蛋白的表达则增加。下调ErbB3和Smad2基因也可降低SK-BR-3和MCF7细胞的侵袭力。我们的结果提示，hrg-β1和ErbB3通过PI3K/Akt-磷酸-Smad2-Snail信号通路诱导SK-BR-3和MCF7乳腺癌细胞的内胚层转移、癌细胞迁移和侵袭。
Heregulin (HRG; also known as neuregulin) is a ligand for ErbB3. One of its isotypes, HRG-β1, binds to ErbB3 and forms heterodimers with other ErbB family members, thereby enhancing the proliferation and tumorigenesis of breast cancer cells. HRG stimulation may contribute to the progression of epithelial–mesenchymal transition (EMT) and tumor metastasis in breast cancer. Majority of studies regarding EMT has been concentrated on TGF-β signaling. Therefore, we investigated whether the HRG-β1 and ErbB3 activate Smad2 signaling during process of EMT in breast cancer cells. The SK-BR-3 and MCF7 breast cancer cell lines were used. The expressions of phospho-Smad2 and EMT markers were observed by western blotting and immunofluorescence assays after treatment with HRG-β1. The cell motility and invasiveness were determined by wound healing and matrigel invasion assays. Smad2 and ErbB3 small interfering RNA (siRNA) transfections were performed to assess the involvement of ErbB3 and Smad2 in HRG-β1-induced EMT. HRG-β1 induced EMT through activation of Smad2. The expression of E-cadherin was decreased after HRG-β1 treatment, while the expressions of Snail, vimentin, and fibronectin were increased. The HRG-β1-induced expressions of Snail, vimentin, and fibronectin, and nuclear colocalization of phospho-Smad2 and Snail were inhibited by pretreatment with a PI3k inhibitor, LY294002, or two phospho-Smad2 inhibitors, PD169316 or SB203580 and cancer cell migration by HRG-β1 was inhibited. Knockdown of Smad2 by siRNA transfection suppressed the expressions of Snail and fibronectin in response to HRG-β1 stimulation and knockdown of ErbB3 suppressed the expressions of phospho-Smad2, Snail, and fibronectin induced by HRG-β1, whereas E-cadherin was increased compared with control siRNA-transfected cells. Knockdown of ErbB3 and Smad2 also decreased SK-BR-3 and MCF7 cell invasion. Our data suggest that HRG-β1 and ErbB3 induce EMT, cancer cell migration and invasion through the PI3k/Akt-phospho-Smad2-Snail signaling pathway in SK-BR-3 and MCF7 breast cancer cells.
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影响因子：
8
作者：
Castagnino, P;Lorenzi, MV;Bottaro, DP
通讯作者：
Bottaro, DP
DOI：
10.1016/j.bbrc.2003.09.021
发表时间：
2003-10-17
影响因子：
3.1
作者：
Fu, YX;O'Connor, LM;Nachtigal, MW
通讯作者：
Nachtigal, MW
转录因子蜗牛和SLUG激活了乳腺癌中转化的生长因子-BETA信号通路。
影响因子：
3.7
作者：
Dhasarathy A;Phadke D;Mav D;Shah RR;Wade PA
通讯作者：
Wade PA
影响因子：
3.7
作者：
Marchini C;Montani M;Konstantinidou G;Orrù R;Mannucci S;Ramadori G;Gabrielli F;Baruzzi A;Berton G;Merigo F;Fin S;Iezzi M;Bisaro B;Sbarbati A;Zerani M;Galiè M;Amici A
通讯作者：
Amici A
影响因子：
2.5
作者：
Godde, Nathan J.;Galea, Ryan C.;Humbert, Patrick O.
通讯作者：
Humbert, Patrick O.