Oncogenesis (Nov 2023)

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

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

DOI
https://doi.org/10.1038/s41389-023-00496-w
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 15

Abstract

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Abstract 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 BRAFV600E mutated-PTCs. That corroborated with the role of RelA and RelB in cell migration and invasion processes that we demonstrated specifically in BRAFV600E 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.