Visfatin promotes cell and tumor growth by upregulating Notch1 in breast cancer.
Visfatin promotes cell and tumor growth by upregulating Notch1 in breast cancer.
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DOI：
10.18632/oncotarget.2086
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发表时间：
2014-07-15
期刊：
影响因子：
--
通讯作者：
Bae SK
中科院分区：
文献类型：
--
作者：
Park HJ;Kim SR;Kim SS;Wee HJ;Bae MK;Ryu MH;Bae SK
Notch1 的过度表达与乳腺癌有关。我们最近发现内脂素可刺激乳腺癌细胞增殖和侵袭。本研究旨在确定 Notch1 信号传导是否受内脂素影响，并表征内脂素-Notch1 轴在乳腺癌中的功能作用。 Visfatin 和 Notch1 在乳腺肿瘤中的表达水平高于匹配的对照组织。 Visfatin 在 MDA-MB-231 乳腺癌细胞系和未转化的 MCF10A 乳腺上皮细胞中诱导 Notch1 表达，而 Visfatin 耗竭则降低了 Notch1 mRNA 和蛋白水平。 MDA-MB-231 细胞中 Notch1 的缺失会减弱细胞在体外和体内的生长；内脏脂肪素消耗也产生类似的效果，但效果较差。此外，Notch1 缺失抑制内脂素诱导的细胞增殖。对 visfatin 介导的 Notch1 上调的信号通路分析表明，visfatin 激活 NF-κB p65。阻断 NF-κB 信号传导可抑制内脂素对 Notch1 上调和乳腺癌细胞增殖的影响。表达高水平 NF-κB p65 的乳腺肿瘤表现出 Notch1 表达增加。我们的结果表明，visfatin-Notch1 轴通过激活 NF-κB 通路促进乳腺肿瘤生长。对visfatin-Notch1轴的研究可能为乳腺癌提供新的治疗方向。
Overexpression of Notch1 has been associated with breast cancer. We recently showed that visfatin stimulates breast cancer cell proliferation and invasion. The present study was undertaken to determine whether Notch1 signaling is affected by visfatin and to characterize the functional role of the visfatin-Notch1 axis in breast cancer. Visfatin and Notch1 were expressed at higher levels in breast tumors than in matched control tissues. Visfatin induced Notch1 expression in MDA-MB-231 breast cancer cell line and in nontransformed MCF10A mammary epithelial cells, whereas visfatin depletion reduced Notch1 mRNA and protein levels. Depletion of Notch1 in MDA-MB-231 cells attenuated cell growth in vitro and in vivo; visfatin depletion produced similar effects, but was less potent. Additionally, Notch1 depletion inhibited cell proliferation induced by visfatin. Analysis of the signaling pathways underlying visfatin-mediated Notch1 upregulation revealed that visfatin activated NF-κB p65. Blockade of NF-κB signaling suppressed the effects of visfatin on Notch1 upregulation and breast cancer cell proliferation. Breast tumors expressing high levels of NF-κB p65 exhibited increased expression of Notch1. Our results demonstrate that the visfatin-Notch1 axis contributes to breast tumor growth through the activation of the NF-κB pathway. Study of the visfatin-Notch1 axis may offer new therapeutic directions for breast cancer.
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