Profiling YB-1 target genes uncovers a new mechanism for MET receptor regulation in normal and malignant human mammary cells

Oncogene. 2009 Mar 19;28(11):1421-31. doi: 10.1038/onc.2008.485. Epub 2009 Jan 19.


Basal-like breast cancers (BLBCs) are aggressive tumors with high relapse rates and poor survival. We recently reported that >70% of primary BLBCs express the oncogenic transcription/translation factor Y-box binding protein-1 (YB-1) and silencing it with small interfering RNAs (siRNAs) attenuates the growth of BLBC cell lines. To understand the basis of these earlier findings, we profiled YB-1:DNA complexes by chromatin immunoprecipitation (ChIP)-on-chip. Several tumor growth-promoting genes such as MET, CD44, CD49f, WNT and NOTCH family members were identified. In addition, YB-1 and MET are coordinately expressed in BLBC cell lines, as well as in normal human mammary progenitor cells. MET was confirmed to be a YB-1 target through traditional ChIP and gel-shift assays. More specifically, YB-1 binds to -1018 bp on the MET promoter. Silencing YB-1 with siRNA decreased MET promoter activity, transcripts, as well as protein levels and signaling. Conversely, expressing wild-type YB-1 or a constitutively active mutant YB-1 (D102) increased MET expression. Finally, silencing YB-1 or MET attenuated anchorage-independent growth of BLBC cell lines. Together, these findings implicate MET as a target of YB-1 that work in concert to promote BLBC growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast / chemistry*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Electrophoretic Mobility Shift Assay
  • Female
  • Gene Expression Profiling
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-met
  • RNA, Small Interfering / genetics
  • Receptors, Growth Factor / analysis
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / physiology*
  • Stem Cells / chemistry
  • Y-Box-Binding Protein 1


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Receptors, Growth Factor
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • Hepatocyte Growth Factor
  • MET protein, human
  • Proto-Oncogene Proteins c-met