ROR1-STAT3信号传递有助于卵巢癌的瘤内异质性
Emilia Piki1, Alice Dini1, Juuli Raivola2
1Disease Networks Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90014, Oulu, Finland.
Cell death discovery
|July 3, 2023
概括
受体氨酸激酶类孤儿受体1 (ROR1) 信号,通过化疗加强,通过STAT3激活驱动卵巢癌 (OC) 的进展. 向ROR1可以克服OC药物耐药性,改善患者的治疗结果.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症信号通路 癌症信号通路
背景情况:
- Wnt通路的失调与各种癌症有关,包括卵巢癌 (OC).
- 非正规的Wnt受体ROR1的异常表达与OC进展和耐药性有关.
- 在OC瘤发生过程中ROR1的精确分子机制尚不清楚.
研究的目的:
- 阐明在卵巢癌进展中由ROR1调解的关键分子事件.
- 调查ROR1信号传递对新辅助化疗的反应中的作用.
- 在OC细胞中识别ROR1的下游作用因子.
主要方法:
- 在新辅助化疗后对ROR1表达变化的分析.
- 在OC细胞中研究Wnt5a/ROR1介导的信号通路 (AKT/ERK/STAT3).
- 在ROR1-敲击OC细胞和临床样本中进行蛋白质学和转录学分析.
- 在独立的OC队列中进行多重免疫组织化学 (mIHC) 验证.
主要成果:
- 在OC中,ROR1的表达通过新辅助化疗被上调.
- 与ROR1结合的Wnt5a通过AKT/ERK/STAT3.3激活瘤原体信号.
- STAT3被确定为ROR1信号的关键下游效应因子.
- ROR1和STAT3在OC瘤的上皮细胞和树皮细胞 (包括CAF) 中共同表达.
结论:
- 由Wnt5a激活并通过化疗增强的ROR1信号,通过STAT3.3促进OC进展.
- ROR1和STAT3在瘤微环境中被共同表达,这表明它们在树皮-上皮相互作用中起作用.
- ROR1代表了克服OC进展和药物耐药性的有希望的治疗标.
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