NF1-Dependent Transcriptome Regulation in the Melanocyte Lineage and in Melanoma

Abstract

The precise role played by the tumor suppressor gene NF1 in melanocyte biology and during the transformation into melanoma is not completely understood. In particular, understanding the interaction during melanocyte development between NF1 and key signaling pathways, which are known to be reactivated in advanced melanoma, is still under investigation. Here, we used RNAseq datasets from either situation to better understand the transcriptomic regulation mediated by an NF1 partial loss of function. We found that NF1 mutations had a differential impact on pluripotency and on melanoblast differentiation. In addition, major signaling pathways such as VEGF, senescence/secretome, endothelin, and cAMP/PKA are likely to be upregulated upon NF1 loss of function in both melanoblasts and metastatic melanoma. In sum, these data bring new light on the transcriptome regulation of the NF1-mutated melanoma subgroup and will help improve the possibilities for specific treatment.

Ethanol Metabolism and Melanoma

“…Ethanol exposure may disrupt a range of melanocyte development processes leading to defective skin pigmentation [130], in which the role of ethanol metabolism is unknown. On the other hand, as previously mentioned in Section 3.1, ethanol increases cAMP/PKA pathway activity, which has been implicated in melanocyte pigmentation, melanomagenesis [131,132], and therapy resistance [133]. Therefore, ethanol may directly affect melanoma initiation and progression.…”