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Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis

Author

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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)

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.

Suggested Citation

  • Wenbin Xu & Han Yao & Zhen Wu & Xiaojun Yan & Zishan Jiao & Yajing Liu & Meng Zhang & Donglai Wang, 2024. "Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45585-5
    DOI: 10.1038/s41467-024-45585-5
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