CCNE1 stabilizes ANLN by counteracting FZR1-mediated the ubiquitination modification to promotes triple negative breast cancer cell stemness and progression by Sujuan Dai & Lin Li & Guangxiu Guo & Yun Peng & Huozhong Yuan & Juntao Li ISBN 101038/S41420025025185 instant download

CCNE1 stabilizes ANLN by counteracting FZR1-mediated the ubiquitination modification to promotes triple negative breast cancer cell stemness and progression by Sujuan Dai & Lin Li & Guangxiu Guo & Yun Peng & Huozhong Yuan & Juntao Li ISBN 101038/S41420025025185 instant download

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies. In this study, we aimed to investigate thepivotal role of cyclin E1 (CCNE1) in the onset and progression of TNBC using comprehensive bioinformatic analysis and functionalvalidation. We found significantly elevated CCNE1 expression in TNBC tissues compared to normal, which correlated with poorprognosis. Functional assessments in vitro and in vivo demonstrated that knockdown of CCNE1 impaired the proliferative,migratory, and invasive capacities of TNBC cells, promoted apoptosis, and reduced tumorigenicity. Furthermore, CCNE1 sustains thestem-like properties of TNBC cells and fuels malignant progression through Anillin (ANLN). Mechanistically, CCNE1 interacted with1234567890();,:ANLN and stabilized its protein levels by counteracting Fizzy-related protein 1 (FZR1)-mediated the ubiquitination modification inTNBC. Mutation of the ubiquitination site in ANLN affected CCNE1’s regulatory functions but not ANLN’s intrinsic properties. Takentogether, these findings underscore the role of CCNE1 in promoting TNBC cell stemness and progression via competitive inhibitionof FZR1-mediated ANLN ubiquitination. Consequently, targeting CCNE1 emerges as a promising therapeutic approach for breastcancer.Cell Death Discovery (2025) 11:228 ;