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The AMPK enzyme, a nexus joined metabolism and cancer. A new therapeutic strategy in cerebral glyoblastomas

17th national competition for scientific and technical research

Metabolism and cancer

Senior Researcher : Rosa Mª Señarís Rodríguez

Research Centre or Institution : Departamento de Fisiología. CIMUS. Universidad de Santiago de Compostela

Abstract

AMP dependent kinase (AMPK) works as a sensor that monitors and maintains energy homeostasis. Although its metabolic function is very well-known, its possible role in cancer has yet to be elucidated. However, there are data that show this enzyme may play a key role in tumoral growth, readjusting cell metabolism to adapt it to oncogenic and metabolic stress, thereby permitting cancerous cells to survive and proliferate. Previous results in our group have shown that glyoblastomas, the main primary tumours of the nervous system, have high levels of AMPK, and that the oncogenic activation of this enzyme is indispensable for the proliferation of these tumoral cells. All of these factors make this molecule a key that could open new therapeutic windows in tumours of this type, for which there is still no effective treatment.

In this project we aim to gain further knowledge of the metabolic function of AMPK in glyoblastomas, under the hypothesis that their function will be of key importance in tumour transformation and progression. For this we will use astrocyte tumours in mice (with oncogenic Rasand/or Pten deletion), and human astrocyte tumours (glyoblastoma and patient tumour lines).

We set ourselves 3 specific objectives:

  1. To determine the role of AMPK in glyoblastoma metabolism. We will centre mainly on glucose metabolism / the Warburg effect, and on anabolic and lipid metabolism, as well as their relationship with hypoxia.
  2. To study the role of AMPK in the metabolic regulation, proliferation and differentiation of glyoblastoma stem cells (GSCs).
  3. To study AMPK inhibitors as new therapeutic strategies against glyoblastomas.
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