PCSK9 promotes progression of anaplastic thyroid cancer through E-cadherin endocytosis by Yu Zhang & Wei Su & Xiaoyu Ji & Zhou Yang & Qing Guan & Yuanxin Pang & Linkun Zhong & Yu Wang & Jun Xiang ISBN 101038/S41419025076901 instant download

PCSK9 promotes progression of anaplastic thyroid cancer through E-cadherin endocytosis by Yu Zhang & Wei Su & Xiaoyu Ji & Zhou Yang & Qing Guan & Yuanxin Pang & Linkun Zhong & Yu Wang & Jun Xiang ISBN 101038/S41419025076901 instant download

Although anaplastic thyroid cancer (ATC) constitutes only 1–2% of all thyroid malignancies, it is associated with an exceptionallyhigh mortality rate, accounting for 14–39% of thyroid cancer-related deaths. In this study, we identified the critical role ofProprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in ATC progression. Proteomic analysis revealed E-cadherin as a key mediatorof PCSK9-driven malignancy in ATC. Mechanistically, PCSK9 promotes the degradation of E-cadherin through the lysosomalpathway. Furthermore, the loss of the p53 function, particularly the R248Q mutation, de-repressed PCSK9 expression at thetranscriptional level. Notably, the PCSK9 inhibitor PF-846 considerably suppressed ATC proliferation and metastasis in both in vitroand in vivo models. In conclusion, PCSK9 enhances ATC malignancy by regulating E-cadherin degradation via the lysosomal1234567890();,:pathway, underscoring its potential as a promising therapeutic target.Cell Death and Disease (2025) 16:362 ;