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The nuclear corepressor 1 and the thyroid hormone receptor β suppress breast tumor lymphangiogenesis

Olaia Martínez-Iglesias1, David Olmeda2, Elvira Alonso-Merino1

  • 1Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Spain.

Oncotarget
|November 3, 2016
PubMed

Insights

Nuclear Receptor Corepressor 1 (NCoR) and thyroid hormone receptor β1 (TRβ) repress breast cancer

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis

Background:

  • Vascular Endothelial Growth Factors C and D (VEGF-C and VEGF-D) drive lymphangiogenesis and breast cancer metastasis.
  • Transcriptional repressors of VEGF-C and VEGF-D are currently unknown.
  • Nuclear Receptor Corepressor 1 (NCoR) and thyroid hormone receptor β1 (TRβ) were previously shown to inhibit tumor invasion.

Purpose of the Study:

  • To investigate the role of NCoR and TRβ in the transcriptional repression of VEGF-C and VEGF-D in breast cancer.
  • To evaluate the therapeutic potential of NCoR and TRβ in inhibiting breast cancer metastasis.

Main Methods:

  • Gene transcription assays in breast cancer cells.
  • Analysis of lymphatic vessel density and lymph node invasion in tumor xenografts.
  • Correlation analysis of NCoR, TRβ, VEGF-C, VEGF-D, and LYVE-1 transcript levels in human breast tumors.

Main Results:

  • NCoR and TRβ were found to repress VEGF-C and VEGF-D gene transcription in breast cancer cells.
  • Repression by NCoR and TRβ reduced lymphatic vessel density and sentinel lymph node invasion in vivo.
  • NCoR and TRβ transcript levels negatively correlated with lymphangiogenic genes and LYVE-1 in human breast tumors.

Conclusions:

  • NCoR and TRβ inhibit breast cancer lymphangiogenesis and metastasis by repressing VEGF-C and VEGF-D transcription.
  • NCoR and TRβ show potential as diagnostic or prognostic biomarkers for breast cancer.
  • NCoR and TRβ warrant further investigation as targets for anti-lymphangiogenic therapy.
Keywords:
VEGFsbreast cancerlymphangiogenesisnuclear receptor corepressor 1thyroid hormone receptor beta 1

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