MIG6 Is MEK-Regulated and Affects EGF-Induced Migration in Mutant NRAS Melanoma

In 2016, a study was conducted to understand the effects of MEK inhibitors in mutant NRAS melanoma, a common driver of cutaneous melanoma. The study used a high-throughput reverse-phase protein array (RPPA) platform to identify signaling alterations. The analysis revealed that in response to trametinib, a MEK inhibitor, there was an increase in AKT signaling and a decrease in the expression of mitogen-inducible gene 6 (MIG6), a negative regulator of EGFR/ERBB receptors. The study found that MIG6 did not affect the growth or survival of mutant NRAS melanoma cells. However, MIG6 was identified as a negative regulator of EGF-induced signaling and cell migration and invasion. In cells where MEK was inhibited, further depletion of MIG6 increased migration and invasion, while MIG6 expression decreased these properties. Therefore, the study concluded that a decrease in MIG6 may promote the migration and invasiveness of MEK-inhibited mutant NRAS melanoma, especially in response to EGF stimulation.