Department of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, Birmingham, Alabama 35205, USA.
J Cell Biochem. 2012 Jan;113(1):13-8. doi: 10.1002/jcb.23350.
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.
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。
