The transcription factor CBFB suppresses breast cancer through orchestrating translation and transcription

Nat Commun. 2019 May 6;10(1):2071. doi: 10.1038/s41467-019-10102-6.


Translation and transcription are frequently dysregulated in cancer. These two processes are generally regulated by distinct sets of factors. The CBFB gene, which encodes a transcription factor, has recently emerged as a highly mutated driver in a variety of human cancers including breast cancer. Here we report a noncanonical role of CBFB in translation regulation. RNA immunoprecipitation followed by deep sequencing (RIP-seq) reveals that cytoplasmic CBFB binds to hundreds of transcripts and regulates their translation. CBFB binds to mRNAs via hnRNPK and enhances translation through eIF4B, a general translation initiation factor. Interestingly, the RUNX1 mRNA, which encodes the transcriptional partner of CBFB, is bound and translationally regulated by CBFB. Furthermore, nuclear CBFB/RUNX1 complex transcriptionally represses the oncogenic NOTCH signaling pathway in breast cancer. Thus, our data reveal an unexpected function of CBFB in translation regulation and propose that breast cancer cells evade translation and transcription surveillance simultaneously through downregulating CBFB.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Core Binding Factor beta Subunit / metabolism*
  • Down-Regulation
  • Eukaryotic Initiation Factors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Heterogeneous-Nuclear Ribonucleoprotein K / metabolism*
  • Humans
  • Mice
  • Mice, Nude
  • RNA, Messenger / metabolism
  • Receptors, Notch / metabolism
  • Signal Transduction / genetics
  • Tissue Array Analysis
  • Xenograft Model Antitumor Assays


  • CBFB protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Core Binding Factor beta Subunit
  • Eukaryotic Initiation Factors
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • RNA, Messenger
  • RUNX1 protein, human
  • Receptors, Notch
  • eIF-4B
  • HNRNPK protein, human