GATA zinc finger protein p66 & beta; promotes breast cancer cell migration by acting as a co-activator of Snail

作者

Zou, XQ; Ma, L; Zhang, YH; Zhang, Q; Xu, C; Zhang, D; Chu, YM; Zhang, J; Li, MY; Zhang, H; Wang, JM; Peng, CC; Wei, G; Wu, YJ; Hou, ZY; Jia, H

作者单位

[Zou, Xiuqun; Zhang, Yihong; Zhang, Qun; Xu, Chu; Zhang, Dan; Zhang, Jie; Li, Mengying; Zhang, Hui; Wang, Jiamin; Hou, Zhaoyuan; Jia, Hao] Shanghai Jiao Tong Univ, Tongren Hosp, Hongqiao Inst Med, Fac Basic Med,Sch Med, Shanghai, Peoples R China; [Zou, Xiuqun; Zhang, Yihong; Zhang, Qun; Xu, Chu; Zhang, Dan; Zhang, Jie; Li, Mengying; Zhang, Hui; Wang, Jiamin; Hou, Zhaoyuan; Jia, Hao] Shanghai Jiao Tong Univ, Dept Biochem & Mol Cellular Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Sch Med, Shanghai, Peoples R China; [Ma, Li; Wei, Gang] Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci, Key Lab Computat Biol, Shanghai, Peoples R China; [Chu, Yimin] Shanghai Jiao Tong Univ, Shanghai Tongren Hosp, Digest Endoscopy Ctr, Sch Med, Shanghai, Peoples R China; [Peng, Chicheng] Naruiboen Biomed Technol Corp Ltd, Linyi, Shandong, Peoples R China; [Wu, Yingjie] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Prov Hosp, Shandong Lab Anim Ctr, Sci & Technol Innovat Ctr, Jinan, Shandong, Peoples R China; [Hou, Zhaoyuan] Chinese Minist Educ, Key Lab Cell Differentiat & Apoptosis, Shanghai, Peoples R China; [Hou, Zhaoyuan] Linyi Univ Shanghai Jiaotong Univ Joint Inst Trans, Linyi, Shandong, Peoples R China

摘要

The transcriptional repressor Snail induces EMT during embryonic development and tumor metastasis. Growing evidence indicates that Snail functions as a trans-activator to induce gene expression; however, the underlying mechanism remains elusive. Here, we report that Snail cooperates with GATA zinc finger protein p66 & beta; to transactivate genes in breast cancer cells. Biologically, depletion of p66 & beta; reduces cell migration and lung metastasis in BALB/c mice. Mechanistically, Snail interacts with p66 & beta; and cooperatively induces gene transcription. Notably, a group of genes induced by Snail harbor conserved G-rich cis-elements (5 & PRIME;-GGGAGG-3 & PRIME;, designated as G-box) in their proximal promoter regions. Snail directly binds to G-box via its zinc fingers and transactivates the G-box-containing promoters. p66 & beta; enhances Snail binding affinity to G-box, whereas depletion of p66 & beta; results in a decreased binding affinity of Snail to the endogenous promoters and concomitantly reduces the transcription of Snail-induced genes. Taken together, these data demonstrated that p66 & beta; is critical for Snail-mediated cell migration by acting as a co-activator of Snail to induce genes containing G-box elements in the promoters.

关键词

基本信息

所属机构:

归属医师: 吴英杰

PMID：37380643

UT：001021100900001

刊名:CELL DEATH & DISEASE

年，卷(期):2023年14卷6期

页码：-null

DOI：10.1038/s41419-023-05887-w

附件： other other

收录: SCIE