一个非正规的Frizzled2通路调节了上皮细胞-介质细胞过渡和转移
Taranjit S Gujral1, Marina Chan1, Leonid Peshkin1
1Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Warren Alpert 524, Boston, MA 02115, USA.
Cell
|November 24, 2014
概括
在转移性癌症中,Frizzled2 (Fzd2) 和Wnt5a/b的含量升高,导致上皮-介质细胞过渡 (EMT) 和细胞迁移. 向Fzd2显示有望抑制瘤生长和转移.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 发育生物学 发展生物学
背景情况:
- Wnt信号对于胚胎发育至关重要.
- Wnt信号的异常与结直肠癌有关.
- 目前正在研究特定Wnt途径组件在转移中的作用.
研究的目的:
- 研究Frizzled2 (Fzd2) 和Wnt5a/b在癌症转移中的作用.
- 阐明Fzd2影响表皮层-介质细胞转换 (EMT) 和细胞迁移的分子机制.
- 在临床前癌症模型中评估针对Fzd2的治疗潜力.
主要方法:
- 在癌细胞系和瘤中分析Fzd2和Wnt5a/b的表达.
- 药理和基因操纵来研究Fzd2的功能.
- 评估EMT标记物,细胞迁移和入侵.
- 在异种移植模型中开发和测试抗Fzd2抗体.
- 基因表达造型,以识别预测性特征.
主要成果:
- 在转移性癌细胞系和高度瘤中,Fzd2和Wnt5a/b被上调调节.
- Fzd2表达与EMT标记器相关联.
- 通过非正规的Fyn/Stat3通路,Fzd2促进EMT和细胞迁移.
- 一个Fzd2调节的基因特征预测患者的转移和生存.
- 一个抗Fzd2抗体抑制了瘤生长,转移,迁移和入侵体内.
结论:
- Fzd2和Wnt5a/b在驱动癌症转移方面发挥着重要作用.
- Fzd2/Fyn/Stat3通路代表了EMT和细胞迁移的新机制.
- 用抗体准Fzd2为转移性癌症提供了一个潜在的治疗策略.
- 这一途径可能有利于患有高Fzd2和Wnt5a/b表达瘤的患者.
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