Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics.
Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics.
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比较蛋白质组学揭示木犀草素通过上调 FZD6 减弱 Wnt 信号传导以抑制前列腺癌干性
DOI：
10.1038/s41598-018-26761-2
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发表时间：
2018-06-04
影响因子：
4.6
通讯作者：
Min D
中科院分区：
文献类型：
--
作者：
Han K;Lang T;Zhang Z;Zhang Y;Sun Y;Shen Z;Beuerman RW;Zhou L;Min D
毛地黄黄酮诱导的抑制前列腺癌（PCa）干性的机制仍然难以捉摸。在这里，我们报告毛地黄黄酮通过上调FZD 6（卷曲类受体6）通过Wnt信号抑制PCa干性。木犀草素在体外抑制前列腺癌细胞增殖、迁移、自我更新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，我们在毛地黄黄酮处理的PC-3细胞中鉴定了208个差异表达蛋白。随后的机制分析表明，毛地黄黄酮抑制Wnt信号通过转录上调FZD 6，从而抑制PCa细胞的干细胞。此外，我们确定FZD 6作为一种肿瘤抑制因子，可以消除PCa干性。总之，我们的研究结果表明，通过上调FZD 6抑制Wnt信号传导是毛地黄黄酮诱导的PCa干性抑制的潜在机制。我们的工作提出了一种针对Wnt信号异常激活引起的人类前列腺癌的新治疗策略。
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 markersin 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.
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影响因子：
4.3
作者：
Park, Shin-Hyung;Park, Hyun Soo;Choi, Yung Hyun
通讯作者：
Choi, Yung Hyun
影响因子：
7.3
作者：
Lang, S. H.;Frame, F. M.;Collins, A. T.
通讯作者：
Collins, A. T.
乳腺癌中毛躁6（FZD6）基因组扩增的功能和预后意义。
DOI：
10.1002/path.4841
发表时间：
2017-02
期刊：
The Journal of pathology
影响因子：
--
作者：
Corda G;Sala G;Lattanzio R;Iezzi M;Sallese M;Fragassi G;Lamolinara A;Mirza H;Barcaroli D;Ermler S;Silva E;Yasaei H;Newbold RF;Vagnarelli P;Mottolese M;Natali PG;Perracchio L;Quist J;Grigoriadis A;Marra P;Tutt AN;Piantelli M;Iacobelli S;De Laurenzi V;Sala A
通讯作者：
Sala A
影响因子：
--
作者：
Selvi RB;Swaminathan A;Chatterjee S;Shanmugam MK;Li F;Ramakrishnan GB;Siveen KS;Chinnathambi A;Zayed ME;Alharbi SA;Basha J;Bhat A;Vasudevan M;Dharmarajan A;Sethi G;Kundu TK
通讯作者：
Kundu TK
影响因子：
16.6
作者：
Huang, Tianzhi;Alvarez, Angel A.;Pangeni, Rajendra P.;Horbinski, Craig M.;Lu, Songjian;Kim, Sung-Hak;James, C. David;Raizer, Jeffery J.;Kessler, John A.;Brenann, Cameron W.;Sulman, Erik P.;Finocchiaro, Gaetano;Tan, Ming;Nishikawa, Ryo;Lu, Xinghua;Nakano, Ichiro;Hu, Bo;Cheng, Shi-Yuan
通讯作者：
Cheng, Shi-Yuan