NF-κB affects proliferation and invasiveness of breast cancer cells by regulating CD44 expression.
NF-κB affects proliferation and invasiveness of breast cancer cells by regulating CD44 expression.
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DOI：
10.1371/journal.pone.0106966
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cai L
中科院分区：
文献类型：
--
作者：
Smith SM;Lyu YL;Cai L
NF-κB在肿瘤的发生和发展中起重要作用。CD 44是一种细胞表面糖蛋白，参与许多细胞过程，包括细胞粘附、迁移和增殖。然而，这两种分子是否以及如何在乳腺癌中相互作用尚不清楚。近年来，CD 44的上调已成为乳腺癌和其他癌症类型中肿瘤起始细胞的标志物。尽管CD 44在细胞过程和癌症中发挥重要作用，但对癌症中CD 44上调的机制仍知之甚少。以前，我们已经确定了一种新的顺式元件，CR 1，位于上游的CD 44启动子。我们证明NF-κB和AP-1是与CR 1相互作用的关键反式作用因子。在此，我们进一步分析了NF-κB在三阴性乳腺癌细胞MDA-MB-231和SUM 159中调节CD 44表达的作用。Bay-11-7082对NF-κB的抑制导致CD 44表达减少。通过抑制NF-κB抑制CD 44从而降低乳腺癌细胞的增殖和侵袭力。这些发现不仅为CD 44调节的分子机制提供了新的见解，而且还提供了可能有助于消除耐化疗和辐射癌细胞的潜在治疗靶点。
NF-κB plays an important role in cancer initiation and progression. CD44, a cell surface glycoprotein, is involved in many cellular processes including cell adhesion, migration and proliferation. However, whether and how the two molecules interact in breast cancer is not clear. In recent years, the up-regulation of CD44 has served as a marker for tumor initiating cells in breast cancer and other cancer types. Despite the important role of CD44 in cellular processes and cancer, the mechanism underlying CD44 up-regulation in cancers remains poorly understood. Previously, we have identified a novel cis-element, CR1, located upstream of the CD44 promoter. We demonstrated that NF-κB and AP-1 are key trans-acting factors that interact with CR1. Here, we further analyzed the role of NF-κB in regulating CD44 expression in triple negative breast cancer cells, MDA-MB-231 and SUM159. Inhibition of NF-κB by Bay-11-7082 resulted in a reduction in CD44 expression. CD44 repression via NF-κB inhibition consequently decreased proliferation and invasiveness of breast cancer cells. These findings provide not only new insight into the molecular mechanism underlying CD44 regulation but also potential therapeutic targets that may help eliminate chemo- and radiation-resistant cancer cells.
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影响因子：
4.8
作者：
Chellaiah, MA;Biswas, RS;Hruska, KA
通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
Breast cancer research : BCR
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