Seminar

Linking metabolic transformation and cell signaling deregulation in cancer

Raul V. Duran, PhD

During last years, a particular attention has been dedicated to examining the crosstalk between metabolism and cell signaling, with especial emphasis in highly proliferating cells. Our investigations focused on how cells sense nutrient availability and how this signal is transduced toward mTOR, a master regulator of cell growth. Our results showed that glutamine, a critical amino acid for the bioenergetics of cancer cells, upregulates mTORC1 pathway through glutaminolyis. Glutaminolysis is the double deamination of glutamine to form α-ketoglutarate. Intracellular α-ketoglutarate stimulates the activity of prolyl hydroxylases (PHDs), necessary for the activation of mTORC1. Therefore, our results established that the glutamine/PHD/mTORC1 pathway constitute a central signaling cascade which regulates cell growth in response to nutrient availability, with important implications in the metabolism of cancer cells.