Discovery of putative tumor suppressors from CRISPR screens reveals rewired lipid metabolism in acute myeloid leukemia cells.

Autor: Lenoir WF; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences; The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Morgado M; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., DeWeirdt PC; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., McLaughlin M; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences; The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Griffith AL; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Sangree AK; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Feeley MN; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Esmaeili Anvar N; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences; The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kim E; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Bertolet LL; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Colic M; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences; The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Dede M; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences; The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Doench JG; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Hart T; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. traver@hart-lab.org.; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. traver@hart-lab.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Nov 11; Vol. 12 (1), pp. 6506. Date of Electronic Publication: 2021 Nov 11.
DOI: 10.1038/s41467-021-26867-8
Abstrakt: CRISPR knockout fitness screens in cancer cell lines reveal many genes whose loss of function causes cell death or loss of fitness or, more rarely, the opposite phenotype of faster proliferation. Here we demonstrate a systematic approach to identify these proliferation suppressors, which are highly enriched for tumor suppressor genes, and define a network of 145 such genes in 22 modules. One module contains several elements of the glycerolipid biosynthesis pathway and operates exclusively in a subset of acute myeloid leukemia cell lines. The proliferation suppressor activity of genes involved in the synthesis of saturated fatty acids, coupled with a more severe loss of fitness phenotype for genes in the desaturation pathway, suggests that these cells operate at the limit of their carrying capacity for saturated fatty acids, which we confirm biochemically. Overexpression of this module is associated with a survival advantage in juvenile leukemias, suggesting a clinically relevant subtype.
(© 2021. The Author(s).)
Databáze: MEDLINE
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