PT  - JOURNAL ARTICLE
AU  - Sanne Marlijn Janssen
AU  - Roy Moscona
AU  - Mounib Elchebly
AU  - Andreas Ioannis Papadakis
AU  - Margaret Redpath
AU  - Hangjun Wang
AU  - Eitan Rubin
AU  - Léon Cornelis van Kempen
AU  - Alan Spatz
TI  - BORIS/CTCFL promotes a switch from a proliferative towards an invasive phenotype in melanoma cells
AID  - 10.1101/560474
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 560474
4099  - http://biorxiv.org/content/early/2019/07/24/560474.short
4100  - http://biorxiv.org/content/early/2019/07/24/560474.full
AB  - 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, though the mechanisms that regulate state transitions are complex and remain poorly understood. 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. Yet, the role of BORIS in melanoma remains elusive. Here, we show that BORIS is involved in melanoma phenotype switching. Genetic modification of BORIS expression in melanoma cells combined with whole transcriptome analysis indicated that BORIS expression contributes to an invasion-associated transcriptome. In line with these findings, inducible BORIS overexpression in melanoma cells reduced proliferation and increased migration and invasion, demonstrating that the transcriptional switch is accompanied by a phenotypic switch. Mechanistically, we reveal that BORIS binds near the promoter of transforming growth factor-beta 1 (TFGB1), a well-recognized factor involved in the transition towards an invasive state, which coincided with increased expression of TGFB1. Overall, our study indicates a pro-invasive role for BORIS in melanoma via transcriptional reprogramming.