甲状腺癌中的NF-κB信号激活和作用:MAP3K14/NIK对MAP3K14/NIK的影响
Françoise Cormier1, Selma Housni2,3, Florent Dumont2,4
1Université Paris Cité, INSERM U1016, CNRS UMR8104, Institut Cochin, F-75014, Paris, France. francoise.cormier@inserm.fr.
核因子-kappa B (NF-κB) 途径在甲状腺癌 (TC) 中被激活,促进瘤的进展. NF-κB诱导激酶 (NIK) 被确定为高级TC的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症信号传递 癌症信号传递
背景情况:
- 毛囊性甲状腺癌 (TC) 具有攻击性行为和耐治疗性,预后不佳.
- 核因子-kappa B (NF-κB) 信号通路与各种癌症的进展有关.
研究的目的:
- 描述TC中的NF-κB通路,并确定新的治疗点.
- 调查NF-κB在瘤进展中的作用,特别是BRAF突变的乳头甲状腺癌 (PTC).
主要方法:
- 免疫块和凝转移试验用于评估TC细胞系中NF-κB通路激活.
- 对TCGA乳头甲状腺癌队列的RNA测序分析.
- 功能性试验评估NF-κB组件在细胞迁移和侵入中的作用.
- 在PTC样本中分析NF-κB诱导激酶 (NIK) 表达.
主要成果:
- 经典和替代NF-κB通路都在TC细胞系中被构成性地激活,形成RelA/p50和RelB/p50二次体.
- 在BRAFV600E突变的PTC中确定了与瘤进展相关的NF-κB特征.
- RelA和RelB促进细胞迁移和入侵,控制MMP1,PLAU,LCN2和LGALS3等基因的表达.
- NF-κB诱导激酶 (NIK) 被确定为TC细胞系中构成性NF-κB激活的新贡献者,并在PTC样本中过度表达.
结论:
- NF-κB通路在TC中被激活,并在瘤细胞入侵中发挥重要作用,特别是在BRAFV600E-突变的PTC中.
- NF-κB诱导激酶 (NIK) 与TC侵入性有关,并且代表了晚期甲状腺癌的潜在治疗标.
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