在转移性三阴性乳腺癌中,RAGE/SNAIL1信号驱动上皮层-介质细胞可塑性
Mireia Pujals1, Carla Mayans1,2, Chiara Bellio1
1Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Oncogene
|July 19, 2023
概括
先进糖化终产品 (RAGE) 信号的受体驱动三阴性乳腺癌 (TNBC) 细胞的可塑性和转移. 抑制RAGE阻断了侵袭并减少了瘤的扩散,为TNBC提供了一个新的治疗点.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 表皮/介质细胞 (E/M) 的可塑性在发育和癌症中至关重要.
- 先进糖化终产品 (RAGE) 的受体影响细胞可塑性,但其在三阴性乳腺癌 (TNBC) 中的作用尚不清楚.
研究的目的:
- 研究RAGE在TNBC细胞可塑性和转移中的作用和分子机制.
- 探索RAGE,TGF-β和TNBC进展中的酸化之间的相互作用.
主要方法:
- 研究了TNBC细胞中的RAGE信号.
- 研究了RAGE抑制对细胞表型,迁移和入侵的影响.
- 模拟了急性化,以评估其对RAGE配体和TNBC细胞入侵的影响.
- 在体内对转移和生存的评估RAGE抑制疗效.
主要成果:
- RAGE信号通过上调 SNAIL1.1 来维持 TNBC 中的介质细胞表型.
- 在TNBC中,TGF-β和RAGE通路之间的交叉对介质细胞特征至关重要.
- 急性酸性增强RAGE连接体的产生和TNBC中的RAGE依赖性入侵.
- 抑制RAGE可以减少TNBC细胞的迁移,入侵和体内转移,从而改善生存率.
结论:
- RAGE信号传递是TNBC中E/M可塑性和转移的关键调节器.
- 向RAGE提供了一个有希望的治疗策略,可以减少TNBC的进展和转移.
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