Department of Medical Oncology, The Affiliated 6th People's Hospital of Shanghai Jiaotong University, Shanghai, 200233, China.
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
Sci Rep. 2018 Jun 4;8(1):8537. doi: 10.1038/s41598-018-26761-2.
The mechanisms underlying luteolin-induced inhibition of prostate cancer (PCa) stemness have remained elusive. Here, we report that luteolin suppresses PCa stemness through Wnt signaling by upregulation of FZD6 (frizzled class receptor 6). Luteolin inhibits PCa cell proliferation, migration, self-renewal as well as the expression of prostate cancer stem cell markers in vitro. Through iTRAQ-based quantitative proteomics study, we identified 208 differentially expressed proteins in luteolin-treated PC-3 cells. Subsequent mechanistic analysis revealed that luteolin inhibits Wnt signaling by transcriptional upregulation of FZD6, and thereby suppressing the stemness of PCa cells. Furthermore, we identified FZD6 as a tumor suppressor that can abolish PCa stemness. In summary, our findings demonstrate that suppression of Wnt signaling by upregulation of FZD6 is a mechanism underlying luteolin-induced inhibition of PCa stemness. Our work suggests a new therapeutic strategy against human prostate cancer caused by aberrant activation of Wnt signaling.
木樨草素抑制前列腺癌（PCa）干细胞特性的机制仍不清楚。在这里，我们报告木樨草素通过上调 FZD6（卷曲蛋白受体 6）抑制 Wnt 信号通路来抑制 PCa 干细胞特性。木樨草素在体外抑制 PCa 细胞增殖、迁移、自我更新以及前列腺癌干细胞标志物的表达。通过基于 iTRAQ 的定量蛋白质组学研究，我们在木樨草素处理的 PC-3 细胞中鉴定出 208 个差异表达蛋白。随后的机制分析表明，木樨草素通过 FZD6 的转录上调抑制 Wnt 信号通路，从而抑制 PCa 细胞的干性。此外，我们鉴定出 FZD6 是一种肿瘤抑制因子，可以消除 PCa 干细胞特性。总之，我们的研究结果表明，通过上调 FZD6 抑制 Wnt 信号通路是木樨草素抑制 PCa 干细胞特性的一种机制。我们的工作为针对 Wnt 信号通路异常激活导致的人类前列腺癌提供了一种新的治疗策略。
