The proto-oncogene tyrosine kinase c-SRC facilitates glioblastoma progression by remodeling fatty acid synthesis.

Glioblastoma / metabolism Humans Proto-Oncogene Mas Fatty Acids / metabolism Cell Line, Tumor Phosphorylation Acetyl Coenzyme A / metabolism Animals CSK Tyrosine-Protein Kinase / metabolism src-Family Kinases / metabolism Disease Progression Mice Brain Neoplasms / metabolism NADP / metabolism Mice, Nude Isocitrate Dehydrogenase / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
28 Aug 2024
Historique:
received: 05 01 2024
accepted: 08 08 2024
medline: 31 8 2024
pubmed: 31 8 2024
entrez: 28 8 2024
Statut: epublish

Résumé

Increased fatty acid synthesis benefits glioblastoma malignancy. However, the coordinated regulation of cytosolic acetyl-CoA production, the exclusive substrate for fatty acid synthesis, remains unclear. Here, we show that proto-oncogene tyrosine kinase c-SRC is activated in glioblastoma and remodels cytosolic acetyl-CoA production for fatty acid synthesis. Firstly, acetate is an important substrate for fatty acid synthesis in glioblastoma. c-SRC phosphorylates acetyl-CoA synthetase ACSS2 at Tyr530 and Tyr562 to stimulate the conversion of acetate to acetyl-CoA in cytosol. Secondly, c-SRC inhibits citrate-derived acetyl-CoA synthesis by phosphorylating ATP-citrate lyase ACLY at Tyr682. ACLY phosphorylation shunts citrate to IDH1-catalyzed NADPH production to provide reducing equivalent for fatty acid synthesis. The c-SRC-unresponsive double-mutation of ACSS2 and ACLY significantly reduces fatty acid synthesis and hampers glioblastoma progression. In conclusion, this remodeling fulfills the dual needs of glioblastoma cells for both acetyl-CoA and NADPH in fatty acid synthesis and provides evidence for glioma treatment by c-SRC inhibition.

Identifiants

DOI: 10.1038/s41467-024-51444-0 PMID: 39198451
pubmed: 39198451
doi: 10.1038/s41467-024-51444-0
pii: 10.1038/s41467-024-51444-0
doi:

Substances chimiques

Proto-Oncogene Mas 0
MAS1 protein, human 0
Fatty Acids 0
Acetyl Coenzyme A 72-89-9
CSK Tyrosine-Protein Kinase EC 2.7.10.2
src-Family Kinases EC 2.7.10.2
CSK protein, human EC 2.7.10.23
NADP 53-59-8
Isocitrate Dehydrogenase EC 1.1.1.41

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7455

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82072777
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32070749
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : U21A20373

Informations de copyright

© 2024. The Author(s).

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Auteurs

Wentao Zhao (W)

Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China. zhaowentao@xmu.edu.cn.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China. zhaowentao@xmu.edu.cn.
ORCID: 0000-0003-4787-5245

Cong Ouyang (C)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Liang Zhang (L)

Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Jinyang Wang (J)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Jiaojiao Zhang (J)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Yan Zhang (Y)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Chen Huang (C)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Qiao Xiao (Q)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Bin Jiang (B)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Furong Lin (F)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Cixiong Zhang (C)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Mingxia Zhu (M)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
ORCID: 0000-0002-1858-5655

Changchuan Xie (C)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
ORCID: 0000-0002-1078-0464

Xi Huang (X)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.

Bingchang Zhang (B)

Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
ORCID: 0000-0002-7655-7257

Wenpeng Zhao (W)

Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Jiawei He (J)

Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Sifang Chen (S)

Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Xiyao Liu (X)

Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Donghai Lin (D)

MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory of Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.

Qinxi Li (Q)

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China. liqinxi@xmu.edu.cn.
ORCID: 0000-0002-7275-4595

Zhanxiang Wang (Z)

Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China. wangzx@xmu.edu.cn.
ORCID: 0000-0003-0405-6194

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Classifications MeSH

questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Glioblastome › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Proto-oncogène Mas › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Lipides › Acides gras › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Métabolisme › Phosphorylation › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides adényliques › Coenzyme A › Acyl coenzyme A › Acétyl coenzyme A › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Eucaryotes › Animaux › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › src-Family kinases › CSK tyrosine-protein kinase › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › src-Family kinases › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides adényliques › NADP › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris nude › The proto-oncogene tyrosine kinase c-SRC...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › NAD (+) and NADP (+) dependent Alcohol oxidoreductases › Isocitrate dehydrogenases › The proto-oncogene tyrosine kinase c-SRC...