M Ríos1, M Foretz2, B Viollet2, A Prieto3, M Fraga4, T García-Caballero4, J A Costoya5, R Señarís6. 1. Departamento de Fisioloxía, CIMUS, IDIS, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain. 2. Inserm, U1016, CNRS UMR8104, Institut Cochin, Université Paris 5, Paris, France. 3. Servicio de Neurociruxía, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain. 4. Departamento de Anatomía Patolóxica e Ciencias Forenses, Universidade de Santiago de Compostela, Santiago de Compostela, Spain. 5. Departamento de Fisioloxía, CIMUS, IDIS, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: josea.costoya@usc.es. 6. Departamento de Fisioloxía, CIMUS, IDIS, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: rosa.senaris@usc.es.
Abstract
AIM OF THE STUDY: 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.
AIM OF THE STUDY: 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 humanastrocytic 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 humanastrocytomas. We then confirmed the results in humanglioblastoma 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: Quan Li; Yanzhen Wang; Guangsheng Cai; Fange Kong; Xiaohan Wang; Yang Liu; Chuanbin Yang; Di Wang; Lirong Teng Journal: Biomed Res Int Date: 2015-11-30 Impact factor: 3.411
Authors: Huanjie Shao; Esraa M Mohamed; Guoyan G Xu; Michael Waters; Kai Jing; Yibao Ma; Yan Zhang; Sarah Spiegel; Michael O Idowu; Xianjun Fang Journal: Oncotarget Date: 2016-01-26