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However, the role of CUL4B in the development of breast cancer remains poorly understood. Here it is shown that CRL4B interacts with multiple histone deacetylase (HDAC)\u2010containing corepressor complexes, including MTA1\/NuRD, SIN3A, CoREST, and NcoR\/SMRT complexes. It is demonstrated that CRL4B\/NuRD(MTA1) complexes cooccupy the E\u2010cadherin and AXIN2 promoters, and could be recruited by transcription factors including Snail and ZEB2 to promote cell invasion and tumorigenesis both in vitro and in vivo. Remarkably, CUL4B responded to transformation and migration\/invasion stimuli and is essential for multiple epithelial\u2010mesenchymal transition (EMT) signaling pathways such as hypoxia. Furthermore, the transcription of CUL4B is directedly activated by hypoxia\u2010inducible factor 1<jats:italic>\u03b1<\/jats:italic> (HIF1<jats:italic>\u03b1<\/jats:italic>) and repressed by the ER<jats:italic>\u03b1<\/jats:italic>\u2010GATA3 axis. Overexpressing of CUL4B successfully induced CSC\u2010like properties. Strikingly, CUL4B expression is markedly upregulated during breast cancer progression and correlated with poor prognosis. The results suggest that CUL4B lies at a critical crossroads between EMT and stem cell properties, supporting CUL4B as a potential novel target for the development of anti\u2010breast cancer therapy.<\/jats:p>","DOI":"10.1002\/advs.202001515","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T08:29:42Z","timestamp":1615883382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["CUL4B Promotes Breast Carcinogenesis by Coordinating with Transcriptional Repressor Complexes in Response to Hypoxia Signaling Pathway"],"prefix":"10.1002","volume":"8","author":[{"given":"Wei","family":"Huang","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Cancer Invasion and Metastasis Research Advanced Innovation Center for Human Brain Protection Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Capital Medical University  Beijing 100069 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