Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells.
Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells.
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DOI：
10.18632/oncotarget.3707
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发表时间：
2015-05-20
期刊：
影响因子：
--
通讯作者：
Nakshatri H
中科院分区：
文献类型：
--
作者：
Burnett RM;Craven KE;Krishnamurthy P;Goswami CP;Badve S;Crooks P;Mathews WP;Bhat-Nakshatri P;Nakshatri H
乳腺癌根据亚型转移到骨、内脏器官和/或脑，这可能涉及转移细胞中宿主器官特异性信号网络的激活。为了验证这种可能性，我们测定了MDA-MB-231细胞及其乳腺脂肪垫肿瘤（TMD-231）、肺转移瘤（LMD-231）、骨转移瘤（BMD-231）、肾上腺转移瘤（ADMD-231）和脑转移瘤（231-BR）变体中的基因表达模式。当比较转移瘤之间的基因表达时，231-BR细胞显示出最高的基因表达差异，其次是ADMD-231、LMD-231和BMD-231细胞。神经元跨膜蛋白SLITRK 2、TMEM 47和LYPD 1在231-BR细胞中特异性过表达。通路分析揭示了使癌细胞能够适应转移器官的信号传导网络的激活，如231-BR中的药物解毒/氧化应激反应/脑信号蛋白神经元通路、ADMD-231中涉及类固醇生成的Notch/孤儿核受体信号、LMD-231中的急性期反应和BMD-231细胞中的细胞因子/造血干细胞信号传导。只有NF-κB信号通路的激活是共同的，除了BMD-231细胞。我们证实NF-κB在231-BR和4 T1细胞的脑转移变体（4 T1-BR）中活化。二甲基氨基蝶呤抑制NF-κB活性、LYPD 1表达及231-BR和4 T1-BR细胞增殖。因此，能够适应宿主器官的转录组变化可能是与器官特异性转移相关的机制之一，并且可能是治疗上的潜在靶点。
Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtype, which may involve activation of a host organ-specific signaling network in metastatic cells. To test this possibility, we determined gene expression patterns in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung-metastasis (LMD-231), bone-metastasis (BMD-231), adrenal-metastasis (ADMD-231) and brain-metastasis (231-BR) variants. When gene expression between metastases was compared, 231-BR cells showed the highest gene expression difference followed by ADMD-231, LMD-231, and BMD-231 cells. Neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1 were specifically overexpressed in 231-BR cells. Pathway-analyses revealed activation of signaling networks that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-κB signaling pathway activation was common to all except BMD-231 cells. We confirmed NF-κB activation in 231-BR and in a brain metastatic variant of 4T1 cells (4T1-BR). Dimethylaminoparthenolide inhibited NF-κB activity, LYPD1 expression, and proliferation of 231-BR and 4T1-BR cells. Thus, transcriptome change enabling adaptation to host organs is likely one of the mechanisms associated with organ-specific metastasis and could potentially be targeted therapeutically.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
拉帕替尼对转移性乳腺癌细胞生长到大脑的影响。
影响因子：
10.3
作者：
Gril, Brunilde;Palmieri, Diane;Bronder, Julie L.;Herring, Jeanne M.;Vega-Valle, Eleazar;Feigenbaum, Lionel;Liewehr, David J.;Steinberg, Seth M.;Merino, Maria J.;Rubin, Stephen D.;Steeg, Patricia S.
通讯作者：
Steeg, Patricia S.
影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
3.7
作者：
Enerly E;Steinfeld I;Kleivi K;Leivonen SK;Aure MR;Russnes HG;Rønneberg JA;Johnsen H;Navon R;Rødland E;Mäkelä R;Naume B;Perälä M;Kallioniemi O;Kristensen VN;Yakhini Z;Børresen-Dale AL
通讯作者：
Børresen-Dale AL