Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis

Wenbin Xu, Han Yao, Zhen Wu, Xiaojun Yan, Zishan Jiao, Yajing Liu, Meng Zhang and Donglai Wang ()
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Wenbin Xu: Chinese Academy of Medical Sciences & Peking Union Medical College
Han Yao: Chinese Academy of Medical Sciences & Peking Union Medical College
Zhen Wu: Chinese Academy of Medical Sciences & Peking Union Medical College
Xiaojun Yan: Chinese Academy of Medical Sciences & Peking Union Medical College
Zishan Jiao: Chinese Academy of Medical Sciences & Peking Union Medical College
Yajing Liu: Chinese Academy of Medical Sciences & Peking Union Medical College
Meng Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Donglai Wang: Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-45585-5

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