Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription.
Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription.
复制标题
锌指蛋白 32 通过直接促进 GPER 转录来促进乳腺癌干细胞样特性
DOI：
10.1038/s41419-018-1144-2
复制
发表时间：
2018-11-26
影响因子：
9
通讯作者：
Wei Y
中科院分区：
文献类型：
--
作者：
Li Y;Gong D;Zhang L;Li H;Zhang S;Zhang J;Li K;Zheng Q;Zhao G;Zhang Y;Chen Y;Guo Y;Xiang R;Lin P;Wei Y
乳腺癌是妇女死亡的主要原因之一。由于存在一小部分干细胞样亚群，一些乳腺癌亚型表现出非常高的恶性度和对多种疗法的耐药性。这些亚型如何获得干细胞样特性并更积极地进展的潜在机制在很大程度上仍然未知。锌指蛋白32（ZNF 32）是一种新发现的转录因子，与乳腺癌的发生、发展密切相关。然而，关于其靶基因及其调控干细胞样特性和耐药性的确切机制仍存在许多问题。在本研究中，我们研究了ZNF 32和GPER（一种膜相关雌激素受体）之间的关系，并讨论了它们在人乳腺癌细胞系中的干细胞调节作用。我们的研究结果表明，ZNF 32可以通过上调GPER表达来诱导干细胞样亚群的扩增并增加耐药性，其中也涉及ERK激活。我们还表明，ZNF 32诱导GPER表达通过ZNF 32的结合序列位于GPER启动子区域。在异种移植小鼠模型中观察到ZNF 32/GPER表达与肿瘤发生率和负荷增加之间的相关性。我们的结论是，ZNF 32可以从事GPER/ERK信号转导，并赋予乳腺癌干细胞样的属性，这可能表明乳腺癌患者的预后不良。ZNF 32和GPER靶向治疗可能为乳腺癌治疗提供新的解决方案。
Breast cancer is one of the leading causes of death in women. Due to the existence of a small fraction of stem cell-like subpopulations, some breast cancer subtypes exhibit very high malignancy and resistance to multiple therapies. The underlying mechanisms of how these subtypes acquire stem cell-like properties and progress more aggressively remain largely unknown. Zinc finger protein 32 (ZNF32), a newly discovered transcription factor, has been reported to be associated with breast cancer progression. However, many questions remain about its target genes and its exact mechanisms in regulating stem cell-like properties and drug resistance. In the present study, we examined the relationship between ZNF32 and GPER, a membrane-associated estrogen receptor, and we addressed their roles in stemness regulation in human breast cancer cell lines. Our results showed that ZNF32 could induce expansion of stem cell-like subpopulations and increase drug resistance by upregulating GPER expression, in which ERK activation was also implicated. We also illustrated that ZNF32 induced GPER expression via a ZNF32 binding sequence located within the GPER promoter region. A correlation between ZNF32/GPER expression and increased tumor incidence and burden was observed in xenograft mouse models. We conclude that ZNF32 can engage GPER/ERK signalling and confer breast cancer stem cell-like properties, which may indicate poor prognosis of breast cancer patients. ZNF32 and GPER targeted therapies might provide new solutions for breast cancer treatment.
登录
查看更多内容
影响因子：
37.3
作者：
Gasch C;Ffrench B;O'Leary JJ;Gallagher MF
通讯作者：
Gallagher MF
ZNF32 通过调节 C1QBP 转录来防止氧化应激诱导的细胞凋亡。
影响因子：
--
作者：
Li K;Gao B;Li J;Chen H;Li Y;Wei Y;Gong D;Gao J;Zhang J;Tan W;Wen T;Zhang L;Huang L;Xiang R;Lin P;Wei Y
通讯作者：
Wei Y
影响因子：
11.2
作者：
Gerweck LE;Wakimoto H
通讯作者：
Wakimoto H
影响因子：
3.8
作者：
Arias-Pulido, Hugo;Royce, Melanie;Gong, Yun;Joste, Nancy;Lomo, Lesley;Lee, Sang-Joon;Chaher, Nabila;Verschraegen, Claire;Lara, Juanita;Prossnitz, Eric R.;Cristofanilli, Massimo
通讯作者：
Cristofanilli, Massimo
ZNF32 通过 mTOR 途径抑制自噬，并保护 MCF-7 细胞免受刺激诱导的细胞死亡。
影响因子：
4.6
作者：
Li Y;Zhang L;Li K;Li J;Xiang R;Zhang J;Li H;Xu Y;Wei Y;Gao J;Lin P;Wei Y
通讯作者：
Wei Y