Role of Bmi-1 in regulation of ionizing irradiation-induced epithelial-mesenchymal transition and migration of breast cancer cells.

Role of Bmi-1 in regulation of ionizing irradiation-induced epithelial-mesenchymal transition and migration of breast cancer cells.
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DOI:
10.1371/journal.pone.0118799
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Wu S
Wu S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yuan W;Yuan Y;Zhang T;Wu S

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放射治疗是一种广泛使用的癌症治疗方法。然而,最近的研究表明,电离辐射(IR)可以促进肿瘤的侵袭和转移。Bmi-1是多梳蛋白家族的一员,已被观察到在一些肿瘤中作为氧化应激的调节剂和促进转移。但其在IR诱导乳腺癌转移中的潜在作用尚未探讨。在我们的研究中,我们发现Bmi-1水平的升高与乳腺癌细胞的EMT有关。通过分析IR诱导乳腺癌的EMT状态和转移,我们发现IR可以抑制或加速乳腺癌细胞的转移潜能,并且具有时间依赖性。沉默Bmi-1完全消除了IR改变、减少或增加乳腺癌细胞迁移的能力。此外,当Bmi-1被敲低时,PI3K/AKT信号对IR影响的EMT的抑制作用被阻断。上述结果表明,Bmi-1是通过激活PI3K/AKT信号通路调控IR诱导乳腺癌细胞EMT和迁移的关键基因;因此,Bmi-1可能是抑制IR引起的转移的新靶点。
Radiotherapy is a widely used treatment for cancer. However, recent studies suggest that ionizing radiation (IR) can promote tumor invasion and metastasis. Bmi-1, a member of the polycomb group protein family, has been observed as a regulator of oxidative stress and promotes metastasis in some tumors. But, its potential role in the metastasis induced by IR of breast cancer has not been explored. In our study, we found that increased levels of Bmi-1 were correlated to EMT of breast cancer cells. Through analyzing the EMT state and metastasis of breast cancer induced by IR, we found the metastatic potential of breast cancer cells can either be inhibited or accelerated by IR following a time-dependent pattern. Silencing Bmi-1 completely abolished the ability of the IR to alter, reduce or increase, the migration of breast cancer cells. Also, when Bmi-1 was knocked down, the effect of inhibition of PI3K/AKT signaling on EMT affected by IR was blocked. These results suggest that Bmi-1 is a key gene in regulation of EMT and migration of breast cancer cells induced by IR through activation of PI3K/AKT signaling; therefore, Bmi-1 could be a new target for inhibiting metastasis caused by IR.
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