Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer

Basal-like breast cancer (BLBC) accounts for approximately 15% of all breast cancer cases, and patients with BLBC have a low survival rate. Our previous study demonstrated that the KLF5 transcription factor promotes BLBC cell proliferation and tumor growth. In this study, we demonstrated that the hi...

Descripción completa

Detalles Bibliográficos
Autores principales: Kong, Yanjie, Ren, Wenlong, Fang, Huan, Shah, Naseer Ali, Shi, Yujie, You, Dingyun, Zhou, Chengang, Jiang, Dewei, Yang, Chuanyu, Liang, Huichun, Liu, Wenjin, Wang, Luzhen, Gan, Wenqiang, Wan, Xing, Li, Fubing, Li, Zhen, Chen, Ceshi, Xie, Ni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935240/
https://www.ncbi.nlm.nih.gov/pubmed/35342356
http://dx.doi.org/10.7150/ijbs.65322
Descripción
Sumario:Basal-like breast cancer (BLBC) accounts for approximately 15% of all breast cancer cases, and patients with BLBC have a low survival rate. Our previous study demonstrated that the KLF5 transcription factor promotes BLBC cell proliferation and tumor growth. In this study, we demonstrated that the histone deacetylase inhibitors (HDACi), suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA), increased KLF5 acetylation at lysine 369 (K369), downregulated KLF5 protein expression levels, and decreased cell viability in BLBC cell lines. HDACi target KLF5 for proteasomal degradation by promoting KLF5 protein ubiquitination. K369 acetylation of KLF5 decreases the binding between KLF5 and its deubiquitinase, BAP1. These findings revealed a novel mechanism by which HDACi suppress BLBC, and a novel crosstalk between KLF5 protein acetylation and ubiquitination.

Ejemplares similares