The nuclear corepressor 1 and the thyroid hormone receptor β suppress breast tumor lymphangiogenesis
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Olaia Martínez-Iglesias1, David Olmeda2, Elvira Alonso-Merino1, Sara Gómez-Rey1, Ana M. González-López1, Enrique Luengo1, María S. Soengas2, José Palacios3, Javier Regadera4, Ana Aranda1
1Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Spain
2Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas, Universidad Autónoma de Madrid, Spain
3Departamento de Anatomía Patológica, Hospital Universitario Ramón y Cajal, Instituto de Investigación Sanitaria Ramón y Cajal (IRYCIS), Universidad de Alcalá, Spain
4Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Spain
Ana Aranda, email: firstname.lastname@example.org
Olaia Martínez Iglesias, email: email@example.com
Keywords: thyroid hormone receptor beta 1, nuclear receptor corepressor 1, lymphangiogenesis, VEGFs, breast cancer
Received: September 01, 2016 Accepted: October 22, 2016 Published: October 27, 2016
Vascular Endotelial Growth Factors C and D (VEGF-C and VEGF-D) are crucial regulators of lymphangiogenesis, a main event in the metastatic spread of breast cancer tumors. Although inhibition of lymphangiogenic gene expression might be a useful therapeutic strategy to restrict the progression of cancer, the factors involved in the transcriptional repression of these genes are still unknown. We have previously shown that Nuclear Receptor Corepressor 1 (NCoR) and the thyroid hormone receptor β1 (TRβ) inhibit tumor invasion. Here we show that these molecules repress VEGF-C and VEGF-D gene transcription in breast cancer cells, reducing lymphatic vessel density and sentinel lymph node invasion in tumor xenografts. The clinical significance of these results is stressed by the finding that NCoR and TRβ transcripts correlate negatively with those of the lymphangiogenic genes and the lymphatic vessel marker LYVE-1 in human breast tumors. Our results point to the use of NCoR and TRβ as potential biomarkers for diagnosis or prognosis in breast cancer and suggest that further studies of these molecules as potential targets for anti-lymphangiogenic therapy are warranted.
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