Heparin-binding growth factor (HDGF) drives radioresistance in breast cancer by activating the STAT3 signaling pathway.
Heparin-binding growth factor (HDGF) drives radioresistance in breast cancer by activating the STAT3 signaling pathway.
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肝素结合生长因子 (HDGF) 通过激活 STAT3 信号通路驱动乳腺癌的放射抗性
DOI：
10.1186/s12967-021-03021-y
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发表时间：
2021-08-10
影响因子：
7.4
通讯作者：
Tang J
中科院分区：
文献类型：
--
作者：
Qiu L;Ma Y;Chen X;Zhou L;Zhang H;Zhong G;Zhang L;Tang J
尽管有报道暗示放射抵抗是乳腺癌治疗的重要障碍，但其分子机制尚不清楚。在此，我们发现高HDGF水平在乳腺癌中显著表达，并与不良生存预后呈正相关。肝素结合生长因子（HDGF）在乳腺癌放射抵抗细胞中表达上调，但其敲低可降低乳腺癌的放射抵抗。此外，RXRα与HDGF启动子的结合阻断了HDGF的转录活性，从而抑制了乳腺癌的放射抗性。HDGF增强的抗辐射活性由TKT和STAT 3诱导，影响STAT 3-Tyr 705和STAT 3-Ser 727磷酸化和STAT 3转录活性。值得注意的是，HDGF消耗使得对靶向STAT 3磷酸化的药物具有放射抗性。这篇文章证明了HDGF作为一个有前途的预测乳腺癌放射抵抗的分子靶点的新功能。
Although reports implicate radioresistance as an important obstacle for the management of breast cancer, its molecular mechanism is elusive. Herein, we found that high HDGF levels are expressed significantly in breast cancer and exhibit a positive association with poor survival prognosis. Heparin-binding growth factor (HDGF) was upregulated in radioresistant breast cancer cells, however, its knockdown could reduce breast cancer radioresistant both in vitro and in vivo. Additionally, the binding of RXRα to HDGF promoter blocked HDGF transcriptional activity, consequently inhibiting breast cancer radioresistance. The enhanced radioresistant activity of HDGF is induced by TKT and STAT3, impacting the STAT3-Tyr705 and STAT3-Ser727 phosphorylation and STAT3 transcriptional activity. Notably, HDGF depletion renders radioresistant hypersensitive to the drug that targets STAT3 phosphorylation. This article demonstrates the novel function of HDGF as a promising molecular target for predicting radioresistance in breast cancer.
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影响因子：
5.8
作者：
Jung, Seung-Nam;Shin, Dae-Seop;Kwon, Byoung-Mog
通讯作者：
Kwon, Byoung-Mog
影响因子：
16.2
作者：
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DOI：
10.1016/s0360-3016(99)00373-9
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2000-01-01
影响因子：
7
作者：
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通讯作者：
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影响因子：
4.8
作者：
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影响因子：
254.7
作者：
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通讯作者：
Jemal, Ahmedin