title: Lipoprotein internalisation induced by oncogenic AMPK activation is essential to maintain glioblastoma cell growth.
abstract: OBJECTIVE
  Metabolic adaptations are essential during tumour growth to maintain the high proliferation levels exhibited by cancer cells. In this study, we examined the transformations that occurred in the lipid metabolism in astrocytic tumours, and the possible role of the fuel-sensing enzyme AMPK. Metabolic targets might help design new and effective drugs for cancer.
  
  
  METHODS
  To accomplish this objective, we studied both mice and human astrocytic tumours. We first used a mouse model of astrocytoma driven by oncogenic H-RasV12 and/or with PTEN deletion based on the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We then confirmed the results in human glioblastoma cell lines and in glioblastoma tissue samples from patients.
  
  
  RESULTS
  We show that the high levels of activated AMPK, observed in astrocytic tumours, increase extracellular lipid internalisation and reduce energy expenditure by inhibiting 'de novo' fatty acid (FA) synthesis, which allows tumour cells to obtain building blocks and energy to be able to create new organelles and new cells.
  
  
  CONCLUSIONS
  Our findings demonstrate that AMPK plays a crucial role in glioblastoma cell growth and suggest that blocking lipoprotein receptors could potentially be used as a plausible therapeutic approach for these and other type of tumours with high levels of AMPK.
authors.affiliation: Departamento de Fisioloxía, CIMUS, IDIS, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ríos
authors.affiliation: Inserm, U1016, CNRS UMR8104, Institut Cochin, Université Paris 5, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Foretz
authors.affiliation: Inserm, U1016, CNRS UMR8104, Institut Cochin, Université Paris 5, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Viollet
authors.affiliation: Servicio de Neurociruxía, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Prieto
authors.affiliation: Departamento de Anatomía Patolóxica e Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Fraga
authors.affiliation: Departamento de Anatomía Patolóxica e Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: T
authors.initials: T
authors.lastname: García-Caballero
authors.affiliation: Departamento de Fisioloxía, CIMUS, IDIS, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: josea.costoya@usc.es.
authors.forename: J A
authors.initials: JA
authors.lastname: Costoya
authors.affiliation: Departamento de Fisioloxía, CIMUS, IDIS, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: rosa.senaris@usc.es.
authors.forename: R
authors.initials: R
authors.lastname: Señarís
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D005227:Fatty Acids / Q000096:biosynthesis; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors; D018110:Receptors, Lipoprotein / Q000037:antagonists & inhibitors / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D005227:Fatty Acids; D018110:Receptors, Lipoprotein; D055372:AMP-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: AMPK; Glioma; Lipid metabolism; Lipoprotein receptors