EVI1 overexpression promotes ovarian cancer progression by regulating estrogen signaling
EVI1 overexpression promotes ovarian cancer progression by regulating estrogen signaling
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DOI：
10.1016/j.mce.2021.111367
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发表时间：
2021-06
影响因子：
4.1
通讯作者：
Zixiang Wang;Yingwei Li;Nan Wang;Peng Li;B. Kong;Zhaojian Liu
中科院分区：
文献类型：
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作者：
Zixiang Wang;Yingwei Li;Nan Wang;Peng Li;B. Kong;Zhaojian Liu
高级别浆液性卵巢癌（HGSOC）的特征是TP 53突变和体细胞拷贝数改变（SCNAs）。在这里，我们表明，致癌转录因子EVI 1（亲嗜性病毒整合位点-1）的扩增和过表达高达30%的1640 HGSOC的情况下，在癌症基因组图谱（TCGA）。在功能上，EVI 1促进体外增殖/侵袭和体内异种移植模型的肿瘤生长。重要的是，我们发现EVI 1通过直接激活ChIP和荧光素酶测定的ESR 1（雌激素受体1）转录来调节雌激素信号传导。有趣的是，EVI 1和ESR 1具有共同的调控靶点，如ChIP-Seq数据分析所示。EVI 1和ESR 1在一些雌激素受体调节基因的调节中起协同作用。此外，EVI 1部分通过调节雌激素信号来驱动肿瘤侵袭性。雌激素促进卵巢癌细胞的增殖、侵袭和异种移植生长。重要的是，雌激素可以挽救由沉默EVI 1诱导的增殖、侵袭和异种移植物生长的抑制。这些发现表明，EVI 1作为卵巢癌雌激素信号网络的一种新的调节剂发挥作用。
High-grade serous ovarian cancer (HGSOC) is characterized by TP53 mutation and somatic copy number alterations (SCNAs). Here we show that the oncogenic transcription factor EVI1 (ecotropic viral integration site-1) is amplified and overexpressed up to 30% of 1640 HGSOC cases in The Cancer Genome Atlas (TCGA). Functionally, EVI1 promotes proliferation/invasionin vitroand tumor growth of xenograft modelin vivo. Importantly, we discover that EVI1 regulates estrogen signaling by directly activating ESR1 (estrogen receptor 1) transcription determined by the ChIP and luciferase assay. Interestingly, EVI1 and ESR1 share common regulatory targets as indicated by the analysis of ChIP-Seq data. EVI1 and ESR1 collaborate in the regulation of some estrogen receptor-regulated genes. Furthermore, EVI1 drives tumor aggressiveness partially by regulating estrogen signaling. Estrogen enhances the proliferation, invasion and xenograft growth of ovarian cancer cells. Importantly, estrogen can rescue the inhibition of proliferation, invasion and xenograft growth induced by silencing EVI1. These findings suggest that EVI1 functions as a novel regulator of the estrogen signaling network in ovarian cancer.