Cytoplasmic accumulation of NCoR in malignant melanoma: consequences of altered gene repression and prognostic significance

Invasive malignant melanoma (MM) usually has a poor prognosis developing visceral disease with no curative therapy available so far. Nuclear corepressor (NCoR) is an essential regulator of gene transcription, and its function is commonly deregulated in different types of cancer. However, little is known on whether and how NCoR loss of function impacts in MM, which might have important diagnostic and prognostic significance. We here show that loss of nuclear NCoR is significantly associated with MM progression, but at comparable stage of the disease is predictive of patient outcome and reduced overall survival. Loss of nuclear NCoR results in upregulation of specific cancer-related genetic signature, whereas inhibition of IKK activity in melanoma cells is reverts both NCoR nuclear distribution and gene transcription. Analysis of public database demonstrated the high prevalence of inactivating NCoR mutations in MM, with characteristics of driver oncogene. 10 samples were analyzed: MMpos (n=4); MMneg (n=3), Ctrl (n=3 )