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

Melanoma is among the most aggressive cancers due to its tendency to metastasize early. Phenotype switching between 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 switching in melanoma. Genetic modification of BORIS expression in melanoma cells combined with whole transcriptome analysis indicated that BORIS expression contributes to an invasion-associated transcriptome. In agreement with this finding, inducible BORIS overexpression in melanoma cells 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 melanoma via transcriptional reprogramming.