Oral Presentation ASDR-AWTRS-MEPSA 2018 Joint Meeting

Impact of nutrient restriction on melanoma progression and response to therapies (#7)

Imanol Arozarena 1
  1. Navarrabiomed, Pamplona, NAVARRA, Spain

Cancer cells rewire their metabolism to promote growth, survival, proliferation and long-term maintenance. The common feature of this altered metabolism is increased glucose uptake in order to fulfil the energetic and biosynthetic requirements that highly proliferating cells demand. In melanoma, enhanced glucose use is favoured through the hyper-activated MAPK pathway, which suppresses OXPHOS and stimulates glycolysis. Despite evidence for the key role glucose plays as an energy source for cancer cells, little is known about the impact of glucose availability on specific proteins or signalling pathways that drive melanoma progression. We discovered that glucose availability controls the melanocytic lineage transcription factor MITF. MITF is a central regulator of melanoma biology and acts as a node between glucose metabolism and cell cycle progression. Besides, glucose restriction induces the transition towards a slow cycling, more aggressive “MITFlow/AXLhigh” phenotype associated with targeted therapy resistance. Previous studies have linked metabolic disorders such as hyperglycemia and diabetes with increased melanoma risk and we are currently exploring the role of glucose restriction in different steps of melanoma development.