PCSK9 promotes progression of anaplastic thyroid cancer through E-cadherin endocytosis.

ABSTRACT: Although anaplastic thyroid cancer (ATC) constitutes only 1-2% of all thyroid malignancies, it is associated with an exceptionally high mortality rate, accounting for 14-39% of thyroid cancer-related deaths. In this study, we identified the critical role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in ATC progression. Proteomic analysis revealed E-cadherin as a key mediator of PCSK9-driven malignancy in ATC. Mechanistically, PCSK9 promotes the degradation of E-cadherin through the lysosomal pathway. Furthermore, the loss of the p53 function, particularly the R248Q mutation, de-repressed PCSK9 expression at the transcriptional level. Notably, the PCSK9 inhibitor PF-846 considerably suppressed ATC proliferation and metastasis in both in vitro and in vivo models. In conclusion, PC

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12056021 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature