Tumor suppressive actions of the nuclear receptor corepressor 1.

ABSTRACT

Nuclear Receptor Corepressor 1 (NCoR) is an important transcriptional regulator that interacts with nuclear receptors and other transcription factors. Recent results have shown the presence of inactivating mutations or deletions of the NCoR gene in human tumors. NCoR has a strong tumor suppressor activity, inhibiting invasion, metastasis formation and tumor growth in xenograft mouse models. These changes are associated to transcriptional inhibition of genes linked to bad prognosis and increased metastasis in cancer patients. NCoR loss causes a long-term repression of NCoR gene transcription, suggesting that NCoR deficiency in the cancer cell could be propagated playing a role in tumor progression in the absence of NCoR gene mutations. The thyroid hormone receptor TRß increases NCoR expression and this induction is essential in mediating the anti-metastatic and tumor suppressive actions of the receptor. Since metastasis is the main cause of cancer-related deaths, these results define NCoR as a potential target for cancer therapy.