ERα Binding by Transcription Factors NFIB and YBX1 Enables FGFR2 Signaling to Modulate Estrogen Responsiveness in Breast Cancer.
ERα Binding by Transcription Factors NFIB and YBX1 Enables FGFR2 Signaling to Modulate Estrogen Responsiveness in Breast Cancer.
复制标题
转录因子NFIB和YBX1的ERα结合使FGFR2信号传导能够调节乳腺癌中的雌激素反应性。
DOI：
10.1158/0008-5472.can-17-1153
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发表时间：
2018-01-15
期刊：
影响因子：
11.2
通讯作者：
Meyer KB
中科院分区：
文献类型：
--
作者：
Campbell TM;Castro MAA;de Oliveira KG;Ponder BAJ;Meyer KB
两个相反的转录因子簇(TF)与雌激素受体阳性或阴性乳腺癌的不同风险有关，但这两个簇相反功能的潜在机制尚不清楚。在这项研究中，我们发现NFIB和YBX1是雌激素受体(ESR1)的新的相互作用因子。NFIB和YBX1都是与ESR1阴性疾病进展相关的风险转铁蛋白。值得注意的是，它们都与ESR1-FOXA1复合体相互作用，并抑制ESR1的反式激活潜力。此外，通过FGFR2的信号传递增强了这些相互作用，并进一步抑制了ESR1靶基因的表达。FGFR2是乳腺癌发生的已知危险因素。因此，我们表明，与ESR1阳性和阴性乳腺癌相关的两组相反的风险TF的成员可以在身体上相互作用。我们推测，这种相互作用形成了受FGFR2信号影响的两条发育途径之间的切换，可能提供了一个用于治疗的连接点。
Two opposing clusters of transcription factors (TFs) have been associated with the differential risks of estrogen receptor positive or negative breast cancers, but the mechanisms underlying the opposing functions of the two clusters are undefined. In this study, we identified NFIB and YBX1 as novel interactors of the estrogen receptor (ESR1). NFIB and YBX1 are both risk TF associated with progression of ESR1-negative disease. Notably, they both interacted with the ESR1-FOXA1 complex and inhibited the transactivational potential of ESR1. Moreover, signaling through FGFR2, a known risk factor in breast cancer development, augmented these interactions and further repressed ESR1 target gene expression. We therefore show that members of two opposing clusters of risk TFs associated with ESR1 positive and negative breast cancer can physically interact. We postulate that this interaction forms a toggle between two developmental pathways affected by FGFR2 signaling, possibly offering a junction to exploit therapeutically.