Editor's Evaluation: Crosstalk with Keratinocytes Causes GNAQ Oncogene Specificity in Melanoma

The study investigated the role of the GNAQQ209L oncogene in melanocytes and its interaction with the epidermal microenvironment, particularly the interfollicular epidermis (IFE). It was found that GNAQQ209L expression in melanocytes led to reduced survival and proliferation in the IFE, attributed to paracrine signaling from keratinocytes, which switched GNAQQ209L from an oncogene to an inhibitor of melanocyte survival. The study highlighted that the epidermal environment played a crucial role in determining the impact of GNAQQ209L, suggesting potential therapies targeting GNAQ and GNA11 mutant melanomas by manipulating these signals. Additionally, GNAQQ209L melanocytes showed increased cell adhesion, disrupted actin cytoskeleton, and a stress response similar to vitiligo, indicating that the microenvironment influenced whether GNAQQ209L signaling was oncogenic or growth-inhibitory.