The Oncoprotein HBXIP Uses Two Pathways to Up-regulate S100A4 in Promotion of Growth and Migration of Breast Cancer Cells*

Background: HBXIP is a novel oncoprotein. Results: HBXIP was able to up-regulate S100A4 though activating STAT4 and inducing DNA methylation of PTEN. Conclusion: HBXIP up-regulates S100A4 via two pathways to promote growth and migration of breast cancer cells. Significance: Our finding provides new insight into the mechanism of HBXIP in promotion of growth and migration of breast cancer. We have reported that hepatitis B X-interacting protein (HBXIP) promotes the proliferation and migration of breast cancer cells. However, the underlying mechanism is poorly understood. In this study, we report that HBXIP works in the event through up-regulating S100A4. We observed that HBXIP expression was positively correlated to that of S100A4 in 87 clinical breast cancer tissue samples. Then, we identified that HBXIP was able to up-regulate S100A4 expression in breast cancer cells. Notably, we observed the HBXIP nuclear localization, implying that HBXIP may be associated with the promoter of S100A4. Chromatin immunoprecipitation assay (ChIP) and electrophoretic mobility shift assay (EMSA) showed that HBXIP was able to bind to the nucleotides +200∼+239 region of S100A4 promoter, containing two putative recognition motif of transcription factor STAT4 and GRβ. It suggests that HBXIP is able to activate S100A4 promoter via interacting with STAT4 in breast cancer cells, leading to the up-regulation of S100A4. In addition, we identified another pathway of S100A4 up-regulation mediated by HBXIP. We found that HBXIP activated the PTEN/PI3K/AKT signaling by inducing DNA methylation of PTEN, which subsequently boosted S100A4 expression. In function, we demonstrated that HBXIP enhanced the growth or migration of breast cancer cells through S100A4 in vivo and in vitro. Collectively, we conclude that HBXIP up-regulates S100A4 through activating S100A4 promoter involving STAT4 and inducing PTEN/PI3K/AKT signaling to promote growth and migration of breast cancer cells. Our finding provides new insight into the mechanism of HBXIP in promotion of the development of breast cancer.

• Publication year

  2012

• Venue

  Journal of Biological Chemistry

• Publication date

  2012-06-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M112.343947PMID 22740693PMCID PMC3436276
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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