SGCE promotes breast cancer stemness by promoting the transcription of FGF-BP1 by Sp1.

SGCE promotes breast cancer stemness by promoting the transcription of FGF-BP1 by Sp1.
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DOI:
10.1016/j.jbc.2023.105351
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发表时间:
2023-11
影响因子:
4.8
通讯作者:
Chen, Ceshi
Chen, Ceshi
中科院分区:
生物学2区
文献类型:
--
作者:
Qiu, Ting;Hou, Lei;Zhao, Lina;Wang, Xinye;Zhou, Zhongmei;Yang, Chuanyu;Zhang, Huifeng;Jiang, Dewei;Jiao, Baowei;Chen, Ceshi

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乳腺癌干细胞是预后不良的主要原因,特别是在三阴性乳腺癌(TNBC)中。在先前的研究中,我们证明了ε-肌聚糖(SGCE),一种Ⅰ型单跨膜蛋白,是一种潜在的癌基因,通过稳定EGFR促进TNBC干性。在这里,我们进一步发现,SGCE消耗减少乳腺癌干细胞,部分通过抑制FGF-BP 1(一种分泌的癌蛋白)的转录。从机制上讲,我们证明SGCE可以与特定的蛋白1转录因子相互作用并易位到细胞核中,这导致FGF-BP 1的转录增加,并且分泌的FBF-BP 1激活FGF-FGFR信号传导以促进癌细胞的干细胞性。新的SGCE-Sp1-FGF-BP 1轴为TNBC提供了新的潜在候选诊断标志物和治疗靶点。
Breast cancer stem cells are mainly responsible for poor prognosis, especially in triple-negative breast cancer (TNBC). In a previous study, we demonstrated that ε-Sarcoglycan (SGCE), a type Ⅰ single-transmembrane protein, is a potential oncogene that promotes TNBC stemness by stabilizing EGFR. Here, we further found that SGCE depletion reduces breast cancer stem cells, partially through inhibiting the transcription of FGF-BP1, a secreted oncoprotein. Mechanistically, we demonstrate that SGCE could interact with the specific protein 1 transcription factor and translocate into the nucleus, which leads to an increase in the transcription of FGF-BP1, and the secreted FBF-BP1 activates FGF-FGFR signaling to promote cancer cell stemness. The novel SGCE-Sp1-FGF-BP1 axis provides novel potential candidate diagnostic markers and therapeutic targets for TNBC.
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