BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript.
BAG3 promotes stem cell-like phenotype in breast cancer by upregulation of CXCR4 via interaction with its transcript.
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BAG3 通过与其转录物相互作用上调 CXCR4，促进乳腺癌干细胞样表型
DOI：
10.1038/cddis.2017.324
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发表时间：
2017-07-13
影响因子：
9
通讯作者：
Wang HQ
中科院分区：
文献类型：
--
作者：
Liu BQ;Zhang S;Li S;An MX;Li C;Yan J;Wang JM;Wang HQ
BAG3是一种进化上保守的高水平表达的共伴侣蛋白，在许多肿瘤类型中具有促进生存的作用。目前的研究报道了BAG3在特定的漂浮培养条件下被诱导，在球体中富集乳腺癌干细胞（BCSC）样细胞。异位BAG3过表达增加CD44+/CD24−CSC亚群，第一代和第二代乳腺球形成，表明BAG3促进乳腺癌中CSC的自我更新和维持。我们进一步证明BAG3在转录后水平上调了CXCR4的表达。进一步研究表明，BAG3与CXCR4 mRNA相互作用，并通过编码区和3 ' -非翻译区促进其表达。在乳腺癌患者中，BAG3也与CXCR4表达及不良预后呈正相关。综上所述，我们的数据表明BAG3通过CXCR4与其转录物的相互作用促进bcsc样表型。因此，本研究确定BAG3是乳腺癌潜在的不良预后因素和治疗靶点。
BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44+/CD24− CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level. Further studies showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its coding and 3′-untranslational regions. BAG3 was also found to be positively correlated with CXCR4 expression and unfavorable prognosis in patients with breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like phenotype through CXCR4 via interaction with its transcript. Therefore, this study establishes BAG3 as a potential adverse prognostic factor and a therapeutic target of breast cancer.
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影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
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DOI：
10.1016/j.bbamcr.2013.10.007
发表时间：
2013-12-01
影响因子：
5.1
作者：
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通讯作者：
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DOI：
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发表时间：
2007-01-01
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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