Lineage-specific silencing of PSAT1 induces serine auxotrophy and sensitivity to dietary serine starvation in luminal breast tumors.

Autor:	Choi BH; Department of Physiology and Biophysics, University of Illinois College of Medicine, 835 South Wolcott Avenue, Room E202 M/C 901, Chicago, IL 60612, USA; University of Illinois Cancer Center, Chicago, IL 60612, USA., Rawat V; Department of Physiology and Biophysics, University of Illinois College of Medicine, 835 South Wolcott Avenue, Room E202 M/C 901, Chicago, IL 60612, USA; University of Illinois Cancer Center, Chicago, IL 60612, USA., Högström J; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Burns PA; Department of Physiology and Biophysics, University of Illinois College of Medicine, 835 South Wolcott Avenue, Room E202 M/C 901, Chicago, IL 60612, USA; University of Illinois Cancer Center, Chicago, IL 60612, USA., Conger KO; Department of Physiology and Biophysics, University of Illinois College of Medicine, 835 South Wolcott Avenue, Room E202 M/C 901, Chicago, IL 60612, USA; University of Illinois Cancer Center, Chicago, IL 60612, USA., Ozgurses ME; Department of Physiology and Biophysics, University of Illinois College of Medicine, 835 South Wolcott Avenue, Room E202 M/C 901, Chicago, IL 60612, USA; University of Illinois Cancer Center, Chicago, IL 60612, USA., Patel JM; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Mehta TS; Department of Radiology, UMass Memorial Medical Center, Worcester, MA 01655, USA., Warren A; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Selfors LM; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Muranen T; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Coloff JL; Department of Physiology and Biophysics, University of Illinois College of Medicine, 835 South Wolcott Avenue, Room E202 M/C 901, Chicago, IL 60612, USA; University of Illinois Cancer Center, Chicago, IL 60612, USA. Electronic address: coloff@uic.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Jan 18; Vol. 38 (3), pp. 110278.
DOI:	10.1016/j.celrep.2021.110278
Abstrakt:	A major challenge of targeting metabolism for cancer therapy is pathway redundancy, in which multiple sources of critical nutrients can limit the effectiveness of some metabolism-targeted therapies. Here, we analyze lineage-dependent gene expression in human breast tumors to identify differences in metabolic gene expression that may limit pathway redundancy and create therapeutic vulnerabilities. We find that the serine synthesis pathway gene PSAT1 is the most depleted metabolic gene in luminal breast tumors relative to basal tumors. Low PSAT1 prevents de novo serine biosynthesis and sensitizes luminal breast cancer cells to serine and glycine starvation in vitro and in vivo. This PSAT1 expression disparity preexists in the putative cells of origin of basal and luminal tumors and is due to luminal-specific hypermethylation of the PSAT1 gene. Our data demonstrate that luminal breast tumors are auxotrophic for serine and may be uniquely sensitive to therapies targeting serine availability. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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