The tumor suppressor RECK interferes with HER-2/Neu dimerization and attenuates its oncogenic signaling

Kun-Jing Hong1, Ming-Chuan Hsu, Ming-Fen Hou

  • 1Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.

FEBS Letters
|January 25, 2011
PubMed

Insights

Reversion-inducing cysteine-rich protein withkazal motifs (RECK) suppresses breast cancer metastasis by inhibiting the HER-2/Neu oncogene. RECK blocks HER-2/Neu receptor dimerization, reducing cancer cell growth and spread.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The HER-2/Neu oncogene promotes tumor metastasis.
  • The role of RECK (Reversion-inducing cysteine-rich protein with kazal motifs) in HER-2/Neu oncogenic function was previously unknown.
  • RECK acts as a tumor metastasis suppressor.

Purpose of the Study:

  • To investigate the effect of RECK on the oncogenic function of HER-2/Neu.
  • To elucidate the molecular mechanisms by which RECK regulates HER-2/Neu signaling.
  • To determine the clinical relevance of RECK expression in breast cancer.

Main Methods:

  • Ectopic expression of RECK in 293T cells and HER-2/Neu-overexpressing breast cancer cells.
  • Co-localization and co-immunoprecipitation assays to study protein interactions.
  • Assessment of HER-2/Neu receptor dimerization and autophosphorylation.
  • Analysis of downstream signaling pathways (ERK, AKT) and target gene expression.
  • Evaluation of RECK expression in human breast cancer tissues and correlation with lymph node invasion.

Main Results:

  • RECK and HER-2/Neu were found to co-localize and interact.
  • RECK inhibited HER-2/Neu receptor dimerization and autophosphorylation.
  • This inhibition led to reduced ERK and AKT kinase activity.
  • Down-regulation of HER-2/Neu target genes was observed.
  • Reduced RECK expression was detected in 58.8% of breast cancer tissues and correlated with lymph node invasion.

Conclusions:

  • RECK negatively regulates the oncogenic activity of HER-2/Neu.
  • RECK inhibits HER-2/Neu signaling by preventing receptor dimerization.
  • RECK functions as an anti-metastatic factor in breast cancer, and its reduced expression is clinically significant.

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