STAT3-survivin signaling mediates a poor response to radiotherapy in HER2-positive breast cancers.
STAT3-survivin signaling mediates a poor response to radiotherapy in HER2-positive breast cancers.
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DOI：
10.18632/oncotarget.6855
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发表时间：
2016-02-09
期刊：
影响因子：
--
通讯作者：
Noh WC
中科院分区：
文献类型：
--
作者：
Kim JS;Kim HA;Seong MK;Seol H;Oh JS;Kim EK;Chang JW;Hwang SG;Noh WC
尽管放射治疗抵抗与乳腺癌局部复发和远处转移相关，但放射抵抗乳腺癌的临床相关分子标志物和关键信号通路尚未确定。在此，我们发现HER 2-STAT 3-生存素调节与HER 2阳性乳腺癌的放疗抵抗相关。通过siRNA消耗HER 2使HER 2阳性乳腺癌细胞对辐射敏感，这是通过降低HER 2阳性乳腺癌细胞中的STAT 3活性和STAT 3靶基因生存素的表达。此外，抑制STAT 3激活或耗尽生存素也使HER 2阳性乳腺癌细胞对辐射敏感，表明HER 2-STAT 3-生存素轴是HER 2阳性乳腺癌细胞放射治疗抗性的关键途径。此外，我们的临床分析证明了HER 2阳性乳腺癌与放疗抵抗之间的关联。值得注意的是，我们发现磷酸化STAT 3，STAT 3和生存素的表达增加与HER 2阳性乳腺癌组织对放疗的不良反应相关。这些发现表明，HER 2-STAT 3-生存素轴可能作为一个预测性标志物和治疗靶点，以克服HER 2阳性乳腺癌的放疗耐药性。
Although radiotherapy resistance is associated with locoregional recurrence and distant metastasis in breast cancers, clinically relevant molecular markers and critical signaling pathways of radioresistant breast cancer are yet to be defined. Herein, we show that HER2-STAT3-survivin regulation is associated with radiotherapy resistance in HER2-positive breast cancers. Depletion of HER2 by siRNA sensitized HER2-positive breast cancer cells to irradiation by decreasing STAT3 activity and survivin, a STAT3 target gene, expression in HER2-positive breast cancer cells. Furthermore, inhibition of STAT3 activation or depletion of survivin also sensitized HER2-positive breast cancer cells to irradiation, suggesting that the HER2-STAT3-survivin axis is a key pathway in radiotherapy resistance of HER2-positive breast cancer cells. In addition, our clinical analysis demonstrated the association between HER2-positive breast cancers and radiotherapy resistance. Notably, we found that increased expression of phosphorylated STAT3, STAT3, and survivin correlated with a poor response to radiotherapy in HER2-positive breast cancer tissues. These findings suggest that the HER2-STAT3-survivin axis might serve as a predictive marker and therapeutic target to overcome radiotherapy resistance in HER2-positive breast cancers.
影响因子：
2.4
作者：
Kim HA;Kim EK;Kim MS;Yu JH;Lee MR;Lee HK;Suh YJ;Noh WC;Korean Breast Cancer Society
通讯作者：
Korean Breast Cancer Society