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CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells

Author

Listed:
  • Jiyeon Kim

    (Children’s Medical Center Research Institute, UT Southwestern Medical Center)

  • Zeping Hu

    (Children’s Medical Center Research Institute, UT Southwestern Medical Center)

  • Ling Cai

    (Children’s Medical Center Research Institute, UT Southwestern Medical Center)

  • Kailong Li

    (Children’s Medical Center Research Institute, UT Southwestern Medical Center)

  • Eunhee Choi

    (UT Southwestern Medical Center)

  • Brandon Faubert

    (Children’s Medical Center Research Institute, UT Southwestern Medical Center)

  • Divya Bezwada

    (Children’s Medical Center Research Institute, UT Southwestern Medical Center)

  • Jaime Rodriguez-Canales

    (University of Texas MD Anderson Cancer Center)

  • Pamela Villalobos

    (University of Texas MD Anderson Cancer Center)

  • Yu-Fen Lin

    (UT Southwestern Medical Center)

  • Min Ni

    (Children’s Medical Center Research Institute, UT Southwestern Medical Center)

  • Kenneth E. Huffman

    (Hamon Center for Therapeutic Oncology, UT Southwestern Medical Center)

  • Luc Girard

    (Hamon Center for Therapeutic Oncology, UT Southwestern Medical Center)

  • Lauren A. Byers

    (University of Texas MD Anderson Cancer Center)

  • Keziban Unsal-Kacmaz

    (Oncology Research Unit, Pfizer)

  • Christopher G. Peña

    (UT Southwestern Medical Center
    University of Texas Health Science Center San Antonio)

  • John V. Heymach

    (University of Texas MD Anderson Cancer Center)

  • Els Wauters

    (University of Gasthuisberg, KU Leuven)

  • Johan Vansteenkiste

    (University of Gasthuisberg, KU Leuven)

  • Diego H. Castrillon

    (UT Southwestern Medical Center)

  • Benjamin P. C. Chen

    (UT Southwestern Medical Center)

  • Ignacio Wistuba

    (University of Texas MD Anderson Cancer Center)

  • Diether Lambrechts

    (Laboratory for Translational Genetics, KU Leuven
    VIB Center for Cancer Biology, KU Leuven)

  • Jian Xu

    (Children’s Medical Center Research Institute, UT Southwestern Medical Center)

  • John D. Minna

    (Hamon Center for Therapeutic Oncology, UT Southwestern Medical Center)

  • Ralph J. DeBerardinis

    (Children’s Medical Center Research Institute, UT Southwestern Medical Center
    UT Southwestern Medical Center
    McDermott Center for Human Growth and Development, UT Southwestern Medical Center)

Abstract

In human cell lines with mutant KRAS and loss of LKB1, CPS1 expression correlates inversely with LKB1 expression; silencing CPS1 in these cells induces DNA damage and cell death as a result of pyrimidine depletion rather than ammonia toxicity.

Suggested Citation

  • Jiyeon Kim & Zeping Hu & Ling Cai & Kailong Li & Eunhee Choi & Brandon Faubert & Divya Bezwada & Jaime Rodriguez-Canales & Pamela Villalobos & Yu-Fen Lin & Min Ni & Kenneth E. Huffman & Luc Girard & L, 2017. "CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells," Nature, Nature, vol. 546(7656), pages 168-172, June.
    • Handle: RePEc:nat:nature:v:546:y:2017:i:7656:d:10.1038_nature22359
    DOI: 10.1038/nature22359
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    Citations

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    Cited by:

    1. Leandro R. Soria & Georgios Makris & Alfonso M. D’Alessio & Angela Angelis & Iolanda Boffa & Veronica M. Pravata & Véronique Rüfenacht & Sergio Attanasio & Edoardo Nusco & Paola Arena & Andrew T. Fere, 2022. "O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Christopher W. Murray & Jennifer J. Brady & Mingqi Han & Hongchen Cai & Min K. Tsai & Sarah E. Pierce & Ran Cheng & Janos Demeter & David M. Feldser & Peter K. Jackson & David B. Shackelford & Monte M, 2022. "LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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