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

Authors: FINKBEINER MR; ASTANEHE A; TO K; FOTOVATI A; DAVIES AH; ZHAO Y; JIANG H; +9 Authors

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

Abstract

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.

Keywords

Chromatin Immunoprecipitation, Hepatocyte Growth Factor, YB-1; Met Receptor; ChIp-on-chip; basal-like breast cancer; mammary progenitors, Gene Expression Profiling, Stem Cells, Nuclear Proteins, Breast Neoplasms, Electrophoretic Mobility Shift Assay, Proto-Oncogene Proteins c-met, DNA-Binding Proteins, Cell Line, Tumor, Proto-Oncogene Proteins, Humans, Female, Receptors, Growth Factor, Breast, Y-Box-Binding Protein 1, RNA, Small Interfering, Promoter Regions, Genetic

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
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    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
84
Top 10%
Top 10%
Top 10%
bronze
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