作者
Diana Putavet, Marjolein Baar, Tao Shi, Johannes Lehmann, Tim Leyten, Esmee Bouma, Antoine Khalil, Harm-Jan Vos, Boudewijn Burgering, Tobias Dansen, Patrick Derksen, Peter de Keizer
发表日期
2022/2/15
期刊
Cancer Research
卷号
82
期号
4_Supplement
页码范围
P1-19-02-P1-19-02
出版商
The American Association for Cancer Research
简介
Metastatic breast cancer is the second most common cause of cancer-related death in women. Triple Negative Breast Cancer (TNBC) has tan especially poor prognosis partly due to these tumors lacking relevant molecular targets. The most commonly mutated gene in TNBC is the tumor suppressor TP53. Mostly, p53 mutations give rise to stably expressed proteins with tumor promoting functions. Therefore, there is an urgent need for therapeutics that can target p53-mutated TNBCs. Here we show that an anti-senescence compound can target metastatic cancers. We found that, in TNBCs, mutant p53 attained a distinctive conformation that has novel oncogenic roles through binding to the transcription factor Forkhead box O (FOXO) 4 sequestered within promyelocytic leukemia (PML) foci. Since these nuclear structures are specific to senescent cells, we tested the senolytic FOXO4 peptide. In cytotoxicity experiments …
学术搜索中的文章