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.

中文翻译：

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BORIS/CTCFL 促进黑色素瘤细胞从增殖型向侵袭型表型的转变。

黑色素瘤由于其早期转移的倾向而成为最具侵袭性的癌症之一。增殖状态和侵袭状态之间的表型转换被认为是转移的关键过程，尽管调节状态转换的机制很复杂并且仍然知之甚少。Brother of Regulator of Imprinted Sites (BORIS)，也称为 CCCTC 结合因子样 (CTCFL)，是一种在黑色素瘤中异常表达的转录调节剂。然而，BORIS 在黑色素瘤中的作用仍然难以捉摸。在这里，我们证明 BORIS 参与黑色素瘤表型转换。黑色素瘤细胞中 BORIS 表达的遗传修饰与全转录组分析相结合表明 BORIS 表达有助于侵袭相关转录组。与这些发现一致，黑色素瘤细胞中可诱导的 BORIS 过度表达减少了增殖并增加了迁移和侵袭，表明转录开关伴随着表型开关。从机制上讲，我们揭示了 BORIS 结合在转化生长因子-β 1 (TFGB1) 的启动子附近，这是一种公认​​的参与向侵袭状态转变的因子，这与 TGFB1 表达的增加相一致。总体而言，我们的研究表明 BORIS 通过转录重编程在黑色素瘤中发挥促侵袭作用。