转移
MMP9公司
癌症研究
转录因子
肺癌
锌指
生物
调节器
基质金属蛋白酶
锌指转录因子
肺
癌症
医学
下调和上调
病理
内科学
基因
遗传学
作者
Wenbin Xu,Han Yao,Zhen Wu,Xiaojun Yan,Zishan Jiao,Yajing Liu,Meng Zhang,Donglai Wang
标识
DOI:10.1038/s41467-024-45585-5
摘要
Abstract Metastasis is the major cause of lung cancer-related death, but the mechanisms governing lung tumor metastasis remain incompletely elucidated. SE translocation (SET) is overexpressed in lung tumors and correlates with unfavorable prognosis. Here we uncover SET-associated transcription factor, zinc finger and BTB domain-containing protein 11 (ZBTB11), as a prometastatic regulator in lung tumors. SET interacts and collaborates with ZBTB11 to promote lung cancer cell migration and invasion, primarily through SET-ZBTB11 complex-mediated transcriptional activation of matrix metalloproteinase-9 (MMP9). Additionally, by transcriptional repression of proline-rich Gla protein 2 (PRRG2), ZBTB11 links Yes-associated protein 1 (YAP1) activation to drive lung tumor metastasis independently of SET-ZBTB11 complex. Loss of ZBTB11 suppresses distal metastasis in a lung tumor mouse model. Overexpression of ZBTB11 is recapitulated in human metastatic lung tumors and correlates with diminished survival. Our study demonstrates ZBTB11 as a key metastatic regulator and reveals diverse mechanisms by which ZBTB11 modulates lung tumor metastasis.
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