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Neutrophils resist ferroptosis and promote breast cancer metastasis through aconitate decarboxylase 1.
Zhao, Yun; Liu, Zhongshun; Liu, Guoqiang; Zhang, Yuting; Liu, Sheng; Gan, Dailin; Chang, Wennan; Peng, Xiaoxia; Sung, Eun Suh; Gilbert, Keegan; Zhu, Yini; Wang, Xuechun; Zeng, Ziyu; Baldwin, Hope; Ren, Guanzhu; Weaver, Jessica; Huron, Anna; Mayberry, Toni; Wang, Qingfei; Wang, Yujue; Diaz-Rubio, Maria Elena; Su, Xiaoyang; Stack, M Sharon; Zhang, Siyuan; Lu, Xuemin; Sheldon, Ryan D; Li, Jun; Zhang, Chi; Wan, Jun; Lu, Xin.
Afiliación
  • Zhao Y; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Liu Z; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Liu G; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre
  • Zhang Y; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre
  • Liu S; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Gan D; Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Chang W; Department of Medical and Molecular Genetics and Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Electrical and Computer Engineering, Purdue University, Indianapolis, IN 46202, USA.
  • Peng X; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Sung ES; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Gilbert K; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Zhu Y; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre
  • Wang X; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Zeng Z; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Baldwin H; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Ren G; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Weaver J; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Huron A; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Mayberry T; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Wang Q; Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Wang Y; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
  • Diaz-Rubio ME; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
  • Su X; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
  • Stack MS; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Zhang S; Department of Pathology, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
  • Lu X; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Sheldon RD; Mass Spectrometry Core, Van Andel Institute, Grand Rapids, MI, USA.
  • Li J; Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA.
  • Zhang C; Department of Medical and Molecular Genetics and Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Electrical and Computer Engineering, Purdue University, Indianapolis, IN 46202, USA.
  • Wan J; Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; School of Informatics and Computing, Indiana University -
  • Lu X; Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre
Cell Metab ; 35(10): 1688-1703.e10, 2023 10 03.
Article en En | MEDLINE | ID: mdl-37793345
ABSTRACT
Metastasis causes breast cancer-related mortality. Tumor-infiltrating neutrophils (TINs) inflict immunosuppression and promote metastasis. Therapeutic debilitation of TINs may enhance immunotherapy, yet it remains a challenge to identify therapeutic targets highly expressed and functionally essential in TINs but under-expressed in extra-tumoral neutrophils. Here, using single-cell RNA sequencing to compare TINs and circulating neutrophils in murine mammary tumor models, we identified aconitate decarboxylase 1 (Acod1) as the most upregulated metabolic enzyme in mouse TINs and validated high Acod1 expression in human TINs. Activated through the GM-CSF-JAK/STAT5-C/EBPß pathway, Acod1 produces itaconate, which mediates Nrf2-dependent defense against ferroptosis and upholds the persistence of TINs. Acod1 ablation abates TIN infiltration, constrains metastasis (but not primary tumors), bolsters antitumor T cell immunity, and boosts the efficacy of immune checkpoint blockade. Our findings reveal how TINs escape from ferroptosis through the Acod1-dependent immunometabolism switch and establish Acod1 as a target to offset immunosuppression and improve immunotherapy against metastasis.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Carboxiliasas / Ferroptosis Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cell Metab Asunto de la revista: METABOLISMO Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Carboxiliasas / Ferroptosis Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cell Metab Asunto de la revista: METABOLISMO Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos