| 论文作者 |
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 |
| 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. |
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