TNFalpha up-regulates SLUG via the NF-kappaB/HIF1alpha axis, which imparts breast cancer cells with a stem cell-like phenotype.
TNFalpha up-regulates SLUG via the NF-kappaB/HIF1alpha axis, which imparts breast cancer cells with a stem cell-like phenotype.
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DOI：
10.1002/jcp.22264
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发表时间：
2010-11
影响因子：
5.6
通讯作者：
Bonafe, Massimiliano
中科院分区：
文献类型：
--
作者：
Storci, Gianluca;Sansone, Pasquale;Mari, Sara;D'uva, Gabriele;Tavolari, Simona;Guarnieri, Tiziana;Taffurelli, Mario;Ceccarelli, Claudio;Santini, Donatella;Chieco, Pasquale;Marcu, Kenneth B.;Bonafe, Massimiliano
肿瘤坏死因子α（TNFα）和核因子-κ B（NF-κB）等细胞外和细胞内炎症介质在乳腺癌的发病、进展和复发中发挥重要作用。SLUG是上皮-间充质转化过程的介导物，在CD 44 +/CD 24 −肿瘤起始乳腺癌细胞和基底样癌中过表达，基底样癌是一种具有干细胞样基因表达谱的侵袭性乳腺癌亚型。癌症干细胞也过度表达促炎性NF-κB网络的成员，但它们与乳腺癌细胞中SLUG表达的功能关系仍不清楚。在这里，我们发现TNFα处理人乳腺癌细胞上调SLUG，依赖于典型的NF-κB/HIF 1 α信号传导，p53失活强烈增强。此外，SLUG上调产生具有干细胞样性质的乳腺癌细胞，包括增强的CD 44和Jagged-1表达以及ERα下调、作为乳腺球生长和细胞外基质侵袭。我们的研究结果揭示了一种分子机制，即TNFα（一种主要的促炎细胞因子）赋予乳腺癌细胞干细胞样特征，这与肿瘤侵袭性增加有关。
Extracellular and intracellular mediators of inflammation, such as Tumor Necrosis Factor alpha (TNFα) and NF-kappaB (NF-κB), play major roles in breast cancer pathogenesis, progression and relapse. SLUG, a mediator of the epithelial-mesenchymal transition process, is over-expressed in CD44+/CD24− tumor initiating breast cancer cells and in basal-like carcinoma, a subtype of aggressive breast cancer endowed with a stem cell-like gene expression profile. Cancer stem cells also over-express members of the pro-inflammatory NF-κB network, but their functional relationship with SLUG expression in breast cancer cells remains unclear. Here, we show that TNFα treatment of human breast cancer cells up-regulates SLUG with a dependency on canonical NF-κB/HIF1α signaling, which is strongly enhanced by p53 inactivation. Moreover, SLUG up-regulation engenders breast cancer cells with stem cell-like properties including enhanced expression of CD44 and Jagged-1 in conjunction with ERα down-regulation, growth as mammospheres and extracellular matrix invasiveness. Our results reveal a molecular mechanism whereby TNFα, a major pro-inflammatory cytokine, imparts breast cancer cells with stem cell-like features, which are connected to increased tumor aggressiveness.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
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影响因子：
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作者：
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作者：
Fulford, L. G.;Easton, D. F.;Hanby, A.
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影响因子：
6.4
作者：
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Purushotham, Anand D.