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Glutamine deprivation triggers NAGK-dependent hexosamine salvage.
Campbell, Sydney; Mesaros, Clementina; Izzo, Luke; Affronti, Hayley; Noji, Michael; Schaffer, Bethany E; Tsang, Tiffany; Sun, Kathryn; Trefely, Sophie; Kruijning, Salisa; Blenis, John; Blair, Ian A; Wellen, Kathryn E.
Afiliación
  • Campbell S; Department of Cancer Biology, University of Pennsylvania, Philadelphia, United States.
  • Mesaros C; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, United States.
  • Izzo L; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States.
  • Affronti H; Department of Cancer Biology, University of Pennsylvania, Philadelphia, United States.
  • Noji M; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, United States.
  • Schaffer BE; Department of Cancer Biology, University of Pennsylvania, Philadelphia, United States.
  • Tsang T; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, United States.
  • Sun K; Department of Cancer Biology, University of Pennsylvania, Philadelphia, United States.
  • Trefely S; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, United States.
  • Kruijning S; Meyer Cancer Center and Department of Pharmacology, Weill Cornell Medicine, New York, United States.
  • Blenis J; Department of Cancer Biology, University of Pennsylvania, Philadelphia, United States.
  • Blair IA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, United States.
  • Wellen KE; Pancreatic Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
Elife ; 102021 11 30.
Article en En | MEDLINE | ID: mdl-34844667
Inside tumors, cancer cells often have to compete with each other for food and other resources they need to survive. This is a key factor driving the growth and progression of cancer. One of the resources cells need is a molecule called UDP-GlcNAc, which they use to modify many proteins so they can work properly. Because cancer cells grow quickly, they likely need much more UDP-GlcNAc than healthy cells. Many tumors, including those derived from pancreatic cancers, have very poor blood supplies, so their cells cannot get the nutrients and other resources they need to grow from the bloodstream. This means that tumor cells have to find new ways to use what they already have. One example of this is developing alternative ways to obtain UDP-GlcNAc. Cells require a nutrient called glutamine to produce UDP-GlcNAc. Limiting the supply of glutamine to cells allows researchers to study how cells are producing UDP-GlcNAc in the lab. Campbell et al. used this approach to study how pancreatic cancer cells obtain UDP-GlcNAc when their access to glutamine is limited. They used a technique called isotope tracing, which allows researchers to track how a specific chemical is processed inside the cell, and what it turns into. The results showed that the pancreatic cancer cells do not make new UDP-GlcNAc but use a protein called NAGK to salvage GlcNAc (another precursor of UDP-GlcNAc), which may be obtained from cellular proteins. Cancer cells that lacked NAGK formed smaller tumors, suggesting that the cells grow more slowly because they cannot recycle UDP-GlcNAc fast enough. Pancreatic cancer is one of the most common causes of cancer deaths and is notable for being difficult to detect and treat. Campbell et al. have identified one of the changes that allows pancreatic cancers to survive and grow quickly. Next steps will include examining the role of NAGK in healthy cells and testing whether it could be targeted for cancer treatment.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Fosfotransferasas (Aceptor de Grupo Alcohol) / Carcinoma Ductal Pancreático / Glutamina / Hexosaminas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Elife Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Fosfotransferasas (Aceptor de Grupo Alcohol) / Carcinoma Ductal Pancreático / Glutamina / Hexosaminas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Elife Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos