| 论文题目: | YB-1 is a Positive Regulator of KLF5 Transcription Factor in Basal-like Breast Cancer |
| 作者: | Jiang, DW ; Qiu, T ; Peng, JJ; Li, SY; Tala; Ren, WL ; Yang, CY; Wen, Y; Chen, CH; Sun, J; Wu, YY; Liu, R ; Zhou, J; Wu, KM; Liu, W; Mao, XY; Zhou, ZM; Chen, CS |
| 联系作者: | chenc@mail.kiz.ac.cn |
| 发表年度: | 2022 |
| DOI: | doi10.1038/s41418-021-00920-x |
| 摘要: | Y-box binding protein 1 (YB-1) is a well-known oncogene highly expressed in various cancers, including basal-like breast cancer (BLBC). Beyond its role as a transcription factor, YB-1 is newly defined as an epigenetic regulator involving RNA 5-methylcytosine. However, its specific targets and pro-cancer functions are poorly defined. Here, based on clinical database, we demonstrate a positive correlation between Kruppel-like factor 5 (KLF5) and YB-1 expression in breast cancer patients, but a negative correlation with that of Dachshund homolog 1 (DACH1). Mechanistically, YB-1 enhances KLF5 expression not only through transcriptional activation that can be inhibited by DACH1, but also by stabilizing KLF5 mRNA in a RNA 5-methylcytosine modification-dependent manner. Additionally, ribosomal S6 kinase 2 (RSK2) mediated YB-1 phosphorylation at Ser102 promotes YB-1/KLF5 transcriptional complex formation, which co-regulates the expression of BLBC specific genes, Keratin 16 (KRT16) and lymphocyte antigen 6 family member D (Ly6D), to promote cancer cell proliferation. The RSK inhibitor, LJH685, suppressed BLBC cell tumourigenesis in vivo by disturbing YB-1-KLF5 axis. Our data suggest that YB-1 positively regulates KLF5 at multiple levels to promote BLBC progression. The novel RSK2-YB-1-KLF5-KRT16/Ly6D axis provides candidate diagnostic markers and therapeutic targets for BLBC |
| 刊物名称: | Cell Death and Differentiation |
| 论文出处: | https://www.nature.com/articles/s41418-021-00920-x |
| 影响因子: | 15.828(2020IF) |
