Decision Letter: Crosstalk with Keratinocytes Causes GNAQ Oncogene Specificity in Melanoma

The study explored the impact of the GNAQQ209L oncogene on melanocytes within the interfollicular epidermis (IFE) of mice, demonstrating that the epidermal microenvironment significantly affected melanocyte behavior. GNAQQ209L expression led to reduced survival due to paracrine signaling from keratinocytes, which inhibited proliferation and promoted apoptosis. However, this effect was reversible, as GNAQQ209L-expressing melanocytes showed increased survival when cultured on fibronectin. In contrast, the epidermal environment enhanced the survival of wildtype and BrafV600E-expressing melanocytes. These findings underscored the crucial role of the microenvironment in determining the oncogenic potential of GNAQQ209L, providing insights that could inform future therapies for GNAQ and GNA11 mutant melanomas.