An AMP-activated protein kinase-PGC-1α axis mediates metabolic plasticity in glioblastoma

Benedikt Sauer; Jan Kueckelhaus; Nadja I. Lorenz; Süleyman Bozkurt; Dorothea Schulte; Jan-Béla Weinem; Mohaned Benzarti; Johannes Meiser; Hans Urban; Giulia Villa; Patrick N. Harter; Christian Münch; Johannes Rieger; Joachim P. Steinbach; Dieter Henrik Heiland; Michael W. Ronellenfitsch

doi:10.1002/ctm2.70030

Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (11) : e70030 DOI: 10.1002/ctm2.70030

RESEARCH ARTICLE

An AMP-activated protein kinase-PGC-1α axis mediates metabolic plasticity in glioblastoma

Benedikt Sauer ¹^,²^,³^,⁴
, Jan Kueckelhaus ⁵^,⁶^,⁷^,⁸^,⁹
, Nadja I. Lorenz ¹^,²^,³^,⁴
, Süleyman Bozkurt ¹⁰
, Dorothea Schulte ¹¹
, Jan-Béla Weinem ¹^,²^,³^,⁴
, Mohaned Benzarti ¹²^,¹³
, Johannes Meiser ¹²^,¹³
, Hans Urban ¹^,²^,³^,⁴
, Giulia Villa ⁵^,⁶^,⁷^,⁸^,⁹
, Patrick N. Harter ¹¹^,¹⁴^,¹⁵
, Christian Münch ⁴^,¹⁰^,¹⁶
, Johannes Rieger ¹^,¹⁷
, Joachim P. Steinbach ¹^,²^,³^,⁴
, Dieter Henrik Heiland ⁵^,⁶^,⁷^,⁸^,⁹
, Michael W. Ronellenfitsch ¹^,²^,³^,⁴^,^†

Author information +

¹. Dr. Senckenberg Institute of Neurooncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany

². University Cancer Center Frankfurt (UCT), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany

³. German Cancer Consortium (DKTK), partner site Frankfurt, a partnership between DKFZ and University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany

⁴. Frankfurt Cancer Institute (FCI), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany

⁵. Microenvironment and Immunology Research Laboratory, Medical Center, University of Freiburg, Freiburg, Germany

⁶. Department of Neurosurgery, Medical Center, University of Freiburg, Freiburg, Germany

⁷. Faculty of Medicine, University of Freiburg, Freiburg, Germany

⁸. Faculty of Medicine and Medical Center, Comprehensive Cancer Center Freiburg (CCCF), University of Freiburg, Freiburg, Germany

⁹. German Cancer Consortium (DKTK), partner site Freiburg, a partnership between DKFZ and University Medical Center Freiburg, Freiburg, Germany

¹⁰. Institute of Molecular Systems Medicine, Faculty of Medicine, Goethe University Frankfurt, Frankfurt am Main, Germany

¹¹. Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt, Germany

¹². Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg

¹³. Faculty of Science, Technology and Medicine, University of Luxembourg, 2 avenue de Université, Esch-sur-Alzette, Luxembourg

¹⁴. German Cancer Consortium (DKTK), partner site Munich, a partnership between DKFZ and Ludwig-Maximilians-Universität (LMU), Munich, Germany

¹⁵. Center for Neuropathology and Prion Research, Faculty of Medicine, Ludwig-Maximilians-Universität (LMU), Munich, Germany

¹⁶. Cardio-Pulmonary Institute, Goethe University Frankfurt, Frankfurt am Main, Germany

¹⁷. Division of Neuro-Oncology, Hertie Institute of Clinical Brain Research, University Hospital Tübingen, Tübingen, Germany

M.Ronellenfitsch@gmx.net

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Abstract

	•AMPK activation induces PGC-1α expression in glioblastoma during nutrient scarcity.
	•PGC-1α enables metabolic plasticity by facilitating metabolism of alternative nutrients in glioblastoma.
	•PGC-1α expression is inversely correlated with hypoxic tumour regions in human glioblastomas.

Keywords

AMP-activated protein kinase / glioblastoma / hypoxia / metabolic plasticity / PGC-1α / PPARGC1A / tumour microenvironment

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Benedikt Sauer,Jan Kueckelhaus,Nadja I. Lorenz,Süleyman Bozkurt,Dorothea Schulte,Jan-Béla Weinem,Mohaned Benzarti,Johannes Meiser,Hans Urban,Giulia Villa,Patrick N. Harter,Christian Münch,Johannes Rieger,Joachim P. Steinbach,Dieter Henrik Heiland,Michael W. Ronellenfitsch. An AMP-activated protein kinase-PGC-1α axis mediates metabolic plasticity in glioblastoma. Clinical and Translational Medicine, 2024, 14(11): e70030 DOI:10.1002/ctm2.70030

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2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.