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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.<\/jats:p>","DOI":"10.1038\/s41467-024-45585-5","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T14:02:45Z","timestamp":1707919365000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis"],"prefix":"10.1038","volume":"15","author":[{"given":"Wenbin","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zishan","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2247-1765","authenticated-orcid":false,"given":"Donglai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"45585_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung, H. et al. 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