Among follicular-derived thyroid cancers (TC), those with aggressive behavior and resistance to current treatments display poor prognosis. NF-κB signaling pathways are involved in tumor progression of various cancers. Here, we finely characterize the NF-κB pathways and their involvement in TC. By using immunoblot and gel shift assays, we demonstrated that both classical and alternative NF-κB pathways are activated in ten TC-derived cell lines, leading to activated RelA/p50 and RelB/p50 NF-κB dimers. By analyzing the RNAseq data of the large papillary thyroid carcinoma (PTC) cohort from The Cancer Genome Atlas (TCGA) project, we identified a tumor progression-related NF-κB signature in BRAF^V600E mutated-PTCs. That corroborated with the role of RelA and RelB in cell migration and invasion processes that we demonstrated specifically in BRAF^V600E mutated-cell lines, together with their role in the control of expression of genes implicated in invasiveness (MMP1, PLAU, LCN2 and LGALS3). We also identified NF-κB-inducing kinase (NIK) as a novel actor of the constitutive activation of the NF-κB pathways in TC-derived cell lines. Finally, its implication in invasiveness and its overexpression in PTC samples make NIK a potential therapeutic target for advanced TC treatment.

在滤泡源性甲状腺癌（TC）中，那些具有侵袭性行为且对当前治疗有抵抗力的患者预后较差。NF-κB信号通路参与多种癌症的肿瘤进展。在这里，我们详细描述了 NF-κB 通路及其在 TC 中的参与。通过使用免疫印迹和凝胶位移测定，我们证明经典和替代 NF-κB 途径在 10 种 TC 衍生细胞系中均被激活，导致 RelA/p50 和 RelB/p50 NF-κB 二聚体被激活。通过分析癌症基因组图谱 (TCGA) 项目中大型甲状腺乳头状癌 (PTC) 队列的 RNAseq 数据，我们在 BRAF V600E^突变PTC 中发现了与肿瘤进展相关的 NF-κB 特征。这证实了我们在 BRAF ^V600E突变细胞系中特别证明的 RelA 和 RelB 在细胞迁移和侵袭过程中的作用，以及它们在控制侵袭性相关基因（MMP1、PLAU、LCN2 和 LGALS3）表达中的作用。 。我们还发现 NF-κB 诱导激酶 (NIK) 是 TC 衍生细胞系中 NF-κB 通路组成型激活的新作用者。最后，NIK 的侵袭性及其在 PTC 样本中的过度表达使 NIK 成为先进 TC 治疗的潜在治疗靶点。