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Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis.
He, Dan; Feng, Huijin; Sundberg, Belen; Yang, Jiaxing; Powers, Justin; Christian, Alec H; Wilkinson, John E; Monnin, Cian; Avizonis, Daina; Thomas, Craig J; Friedman, Richard A; Kluger, Michael D; Hollingsworth, Michael A; Grandgenett, Paul M; Klute, Kelsey A; Toste, F Dean; Chang, Christopher J; Chio, Iok In Christine.
Afiliación
  • He D; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Feng H; Institute for Cancer Genetics, Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Sundberg B; Institute for Cancer Genetics, Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Yang J; Institute for Cancer Genetics, Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Powers J; Institute for Cancer Genetics, Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Christian AH; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Wilkinson JE; University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Monnin C; Metabolomics Innovation Resource, Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada.
  • Avizonis D; Metabolomics Innovation Resource, Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC H3A 1A3, Canada.
  • Thomas CJ; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Friedman RA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Kluger MD; Division of Gastrointestinal & Endocrine Surgery, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
  • Hollingsworth MA; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Grandgenett PM; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Klute KA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Toste FD; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Chang CJ; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: chrischang@berkeley.edu.
  • Chio IIC; Institute for Cancer Genetics, Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: christine.chio@columbia.edu.
Mol Cell ; 82(16): 3045-3060.e11, 2022 08 18.
Article en En | MEDLINE | ID: mdl-35752173
Cancer mortality is primarily a consequence of its metastatic spread. Here, we report that methionine sulfoxide reductase A (MSRA), which can reduce oxidized methionine residues, acts as a suppressor of pancreatic ductal adenocarcinoma (PDA) metastasis. MSRA expression is decreased in the metastatic tumors of PDA patients, whereas MSRA loss in primary PDA cells promotes migration and invasion. Chemoproteomic profiling of pancreatic organoids revealed that MSRA loss results in the selective oxidation of a methionine residue (M239) in pyruvate kinase M2 (PKM2). Moreover, M239 oxidation sustains PKM2 in an active tetrameric state to promote respiration, migration, and metastasis, whereas pharmacological activation of PKM2 increases cell migration and metastasis in vivo. These results demonstrate that methionine residues can act as reversible redox switches governing distinct signaling outcomes and that the MSRA-PKM2 axis serves as a regulatory nexus between redox biology and cancer metabolism to control tumor metastasis.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Hormonas Tiroideas / Proteínas Portadoras / Carcinoma Ductal Pancreático / Proteínas de la Membrana Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Hormonas Tiroideas / Proteínas Portadoras / Carcinoma Ductal Pancreático / Proteínas de la Membrana Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos