Abstract 1362 GNAQ/11-driven melanoma is safeguarded against calcium overload by a phosphatase that degrades inositol (1,4,5)-trisphosphate

Mutations that constitutively activate G proteins encoded by GNAQ or GNA11 are the oncogenic drivers in a subset of cutaneous melanomas and greater than 90% of ocular (uveal) melanomas (UM). These mutant G proteins constitutively activate a signaling pathway resulting in extraordinarily high-flux production of inositol (1,4,5)-trisphosphate (IP3), which releases calcium from the endoplasmic reticulum (ER) and triggers store-operated calcium entry (SOCE). Because chronically high levels of intracellular calcium are lethal, the goal of this study was to identify mechanisms responsible for the paradoxical survival of melanoma cells in the face of high IP3 flux.