突变体
转移
癌症研究
转录因子
生物
乳腺癌
癌症
基因
遗传学
作者
Sike Hu,Manxue Wang,Ailing Ji,Jie Ye,Ruifang Gao,Xia Li,Li Sun,Jing Wang,Lihong Ye,Hongbin Liu
出处
期刊:FEBS Letters
[Wiley]
日期:2023-11-23
卷期号:597 (24): 3087-3101
标识
DOI:10.1002/1873-3468.14774
摘要
Tumor‐associated p53 mutations induce activities different from wild‐type p53, thus causing loss of the protein's tumor inhibition function. The cells carrying p53 mutations have more aggressive characteristics related to invasion, metastasis, proliferation, and cell survival. By comparing the gene expression profiles of mutant p53 (mutp53) and mutp53 silenced cohorts, we found that FOS‐related antigen‐1 (FRA‐1), which is encoded by FOSL1 , is a potential effector of mutp53‐mediated metastasis. We demonstrate that the expression of FRA‐1, a gatekeeper of mesenchymal–epithelial transition, is elevated in the presence of p53 mutations. Mechanistically, mutant p53 cooperates with the transcription factor ELK1 in binding and activating the promoter of FOSL1, thus fostering lung metastasis. This study reveals new insights into how mutant p53 contributes to metastasis in breast cancer.
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