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Article Dans Une Revue Oncogenesis Année : 2023

NF-κB signaling activation and roles in thyroid cancers: implication of MAP3K14/NIK

Selma Housni
  • Fonction : Auteur
Florent Dumont
  • Fonction : Auteur
Mélodie Villard
  • Fonction : Auteur
Béatrix Cochand-Priollet
  • Fonction : Auteur
Françoise Mercier-Nomé
  • Fonction : Auteur
Karine Perlemoine
  • Fonction : Auteur
Jérôme Bertherat
Lionel Groussin
  • Fonction : Auteur

Résumé

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-κBinducing 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.
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Dates et versions

hal-04301967 , version 1 (23-11-2023)

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Françoise Cormier, Selma Housni, Florent Dumont, Mélodie Villard, Béatrix Cochand-Priollet, et al.. NF-κB signaling activation and roles in thyroid cancers: implication of MAP3K14/NIK. Oncogenesis, 2023, 12 (1), pp.55. ⟨10.1038/s41389-023-00496-w⟩. ⟨hal-04301967⟩

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