BORIS/CTCFL promotes a switch from a proliferative towards an invasive phenotype in melanoma cell lines

Melanomais among the most aggressive cancers due to its tendency to metastasize early. Phenotype switchingbetween a proliferative and an invasive state has been suggested as a critical process for metastasis. The mechanisms that regulate these transitions are poorly understood, but are associated with transcriptional changes. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcriptional modulator that becomes aberrantly expressed in melanoma. Here, we provide the first evidence that BORIS is involved in phenotype switchingin melanoma. Genetic modification of BORIS expression in melanomacells combined with whole transcriptomeanalysis indicated that BORIS expression contributes to an invasion-associated transcriptome. In agreement with this finding, inducible BORIS overexpression in melanomacells reduced proliferation and increased migration and invasion, demonstrating that the transcriptional switch is accompanied by a phenotypic switch. Overall, our study indicates a pro-invasive role for BORIS in melanomavia transcriptional reprogramming.