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

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, Lauren A. Byers, Keziban Unsal-Kacmaz, Christopher G. Peña, John V. Heymach, Els Wauters, Johan Vansteenkiste, Diego H. Castrillon, Benjamin P. C. Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D. Minna and Ralph J. DeBerardinis ()
Additional contact information
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
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
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

Nature, 2017, vol. 546, issue 7656, 168-172

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.

Date: 2017
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DOI: 10.1038/nature22359

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