GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity.

Autor:	Watson DC; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Case Comprehensive Cancer Center, Cleveland, OH, USA.; University Hospitals Cleveland Medical Center, Cleveland, OH, USA.; School of Medicine, Case Western Reserve University, Cleveland, OH, USA.; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA., Bayik D; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Case Comprehensive Cancer Center, Cleveland, OH, USA.; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA., Storevik S; Department of Biomedicine, University of Bergen, Bergen, Norway.; Department of Neurology, Haukeland University Hospital, Bergen, Norway., Moreino SS; Department of Biomedicine, University of Bergen, Bergen, Norway., Sprowls SA; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Han J; Department of Biomedicine, University of Bergen, Bergen, Norway., Augustsson MT; Department of Biomedicine, University of Bergen, Bergen, Norway., Lauko A; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA.; Medical Scientist Training Program, Case Western Reserve University, Cleveland, OH, USA., Sravya P; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA., Røsland GV; Department of Biomedicine, University of Bergen, Bergen, Norway., Troike K; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Tronstad KJ; Department of Biomedicine, University of Bergen, Bergen, Norway., Wang S; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Sarnow K; Department of Biomedicine, University of Bergen, Bergen, Norway., Kay K; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Lunavat TR; Department of Biomedicine, University of Bergen, Bergen, Norway.; Department of Neurology, Molecular Neurogenetics Unit-West, Massachusetts General Hospital, Boston, MA, USA., Silver DJ; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Dayal S; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Joseph JV; Stipe Therapeutics, Aarhus, Denmark., Mulkearns-Hubert E; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA., Ystaas LAR; Department of Biomedicine, University of Bergen, Bergen, Norway., Deshpande G; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Guyon J; University of Bordeaux, INSERM, BRIC, Pessac, France., Zhou Y; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Magaut CR; University of Bordeaux, INSERM, BRIC, Pessac, France., Seder J; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Neises L; Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg., Williford SE; University of Alabama at Birmingham, Birmingham, AL, USA., Meiser J; Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg., Scott AJ; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA., Sajjakulnukit P; Cancer Biology Graduate Program, University of Michigan, Ann Arbor, MI, USA., Mears JA; Case Comprehensive Cancer Center, Cleveland, OH, USA.; School of Medicine, Case Western Reserve University, Cleveland, OH, USA., Bjerkvig R; Department of Biomedicine, University of Bergen, Bergen, Norway.; NorLux Neuro-Oncology Laboratory, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg., Chakraborty A; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Case Comprehensive Cancer Center, Cleveland, OH, USA., Daubon T; University of Bordeaux, CNRS, IBGC, Bordeaux, France., Cheng F; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.; Case Comprehensive Cancer Center, Cleveland, OH, USA., Lyssiotis CA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA., Wahl DR; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA., Hjelmeland AB; University of Alabama at Birmingham, Birmingham, AL, USA., Hossain JA; Department of Biomedicine, University of Bergen, Bergen, Norway., Miletic H; Department of Biomedicine, University of Bergen, Bergen, Norway. hrvoje.miletic@uib.no.; Department of Pathology, Haukeland University Hospital, Bergen, Norway. hrvoje.miletic@uib.no., Lathia JD; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. lathiaj@ccf.org.; Case Comprehensive Cancer Center, Cleveland, OH, USA. lathiaj@ccf.org.; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA. lathiaj@ccf.org.
Jazyk:	angličtina
Zdroj:	Nature cancer [Nat Cancer] 2023 May; Vol. 4 (5), pp. 648-664. Date of Electronic Publication: 2023 May 11.
DOI:	10.1038/s43018-023-00556-5
Abstrakt:	The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications of mitochondria transfer on tumor biology are poorly understood. Here we show that mitochondria transfer is a prevalent phenomenon in glioblastoma (GBM), the most frequent and malignant primary brain tumor. We identified horizontal mitochondria transfer from astrocytes as a mechanism that enhances tumorigenesis in GBM. This transfer is dependent on network-forming intercellular connections between GBM cells and astrocytes, which are facilitated by growth-associated protein 43 (GAP43), a protein involved in neuron axon regeneration and astrocyte reactivity. The acquisition of astrocyte mitochondria drives an increase in mitochondrial respiration and upregulation of metabolic pathways linked to proliferation and tumorigenicity. Functionally, uptake of astrocyte mitochondria promotes cell cycle progression to proliferative G2/M phases and enhances self-renewal and tumorigenicity of GBM. Collectively, our findings reveal a host-tumor interaction that drives proliferation and self-renewal of cancer cells, providing opportunities for therapeutic development. (© 2023. The Author(s).)
Databáze:	MEDLINE
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