Wnt/β-catenin 信号通路：三阴性乳腺癌治疗的潜在治疗靶点。
The Wnt/β-catenin signaling pathway: a potential therapeutic target in the treatment of triple negative breast cancer.
机构信息
Department of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, Birmingham, Alabama 35205, USA.
出版信息
J Cell Biochem. 2012 Jan;113(1):13-8. doi: 10.1002/jcb.23350.
Abstract
Breast cancer continues to be a serious health problem particularly in developed countries. Of particular concern is triple negative breast cancer (TNBC) which does not respond well to standard hormone therapy and is associated with poor overall patient prognosis. Recent studies indicate that Wnt/β-catenin signaling is particularly activated in TNBC, such that the Wnt receptor frizzled-7 (FZD7) and the Wnt co-receptor LRP6 were found to be up regulated in TNBC. In addition, it has been demonstrated that transcriptional knockdown of LRP6 or FZD7 in TNBC cells suppressed tumor growth in vivo. Furthermore, salinomycin, a selective breast cancer stem cell killer, was recently demonstrated to be an inhibitor of Wnt/β-catenin signaling by inducing LRP6 degradation. Therefore, the Wnt/β-catenin signaling pathway and particularly the Wnt receptors on the cell surface may serve as novel therapeutic targets for the treatment of TNBC.
摘要
乳腺癌仍然是一个严重的健康问题，特别是在发达国家。特别值得关注的是三阴性乳腺癌（TNBC），它对标准激素治疗反应不佳，且总体患者预后较差。最近的研究表明，Wnt/β-catenin 信号在 TNBC 中特别活跃，因此 Wnt 受体卷曲蛋白 7（FZD7）和 Wnt 共受体 LRP6 被发现在上调 TNBC。此外，已经证明在 TNBC 细胞中敲低 LRP6 或 FZD7 的转录可以抑制体内肿瘤生长。此外，最近的研究表明，盐霉素是一种选择性的乳腺癌干细胞杀伤剂，通过诱导 LRP6 降解来抑制 Wnt/β-catenin 信号通路。因此，Wnt/β-catenin 信号通路，特别是细胞表面上的 Wnt 受体，可能成为治疗 TNBC 的新的治疗靶点。
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1
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Cancer Lett. 2011 Dec 1;311(1):113-21. doi: 10.1016/j.canlet.2011.07.016. Epub 2011 Jul 21.
2
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Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13253-7. doi: 10.1073/pnas.1110431108. Epub 2011 Jul 25.
3
Rspo2/Int7 regulates invasiveness and tumorigenic properties of mammary epithelial cells.Rspo2/Int7 调节乳腺上皮细胞的侵袭和致瘤特性。
J Cell Physiol. 2012 May;227(5):1960-71. doi: 10.1002/jcp.22924.
4
Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling.Lgr5 同源物与 Wnt 受体结合并介导 R-spondin 信号通路。
Nature. 2011 Jul 4;476(7360):293-7. doi: 10.1038/nature10337.
5
R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling.R 分泌蛋白作为孤儿受体 LGR4 和 LGR5 的配体，调节 Wnt/β-连环蛋白信号通路。
Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11452-7. doi: 10.1073/pnas.1106083108. Epub 2011 Jun 21.
6
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Oncogene. 2011 Oct 27;30(43):4437-46. doi: 10.1038/onc.2011.145. Epub 2011 May 2.
7
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Mod Pathol. 2011 Feb;24(2):209-31. doi: 10.1038/modpathol.2010.205. Epub 2010 Nov 12.
8
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Nat Rev Clin Oncol. 2010 Dec;7(12):683-92. doi: 10.1038/nrclinonc.2010.154. Epub 2010 Sep 28.
9
Wnt isoform-specific interactions with coreceptor specify inhibition or potentiation of signaling by LRP6 antibodies.Wnt 同工型与共受体的特异性相互作用决定了 LRP6 抗体对信号的抑制或增强作用。
PLoS One. 2010 Sep 13;5(9):e12682. doi: 10.1371/journal.pone.0012682.
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