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@ARTICLE{Lee:166539,
author = {W. D. Lee and A. C. Pirona$^*$ and B. Sarvin and A. Stern
and K. Nevo-Dinur and E. Besser and N. Sarvin and S. Lagziel
and D. Mukha and S. Raz and E. Aizenshtein and T. Shlomi},
title = {{T}umor {R}eliance on {C}ytosolic versus {M}itochondrial
{O}ne-{C}arbon {F}lux {D}epends on {F}olate {A}vailability.},
journal = {Cell metabolism},
volume = {33},
number = {1},
issn = {1550-4131},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DKFZ-2020-02982},
pages = {190-198.e6},
year = {2021},
note = {2021 Jan 5;33(1):190-198.e6 / #DKFZ-MOST-Ca173#},
abstract = {Folate metabolism supplies one-carbon (1C) units for
biosynthesis and methylation and has long been a target for
cancer chemotherapy. Mitochondrial serine catabolism is
considered the sole contributor of folate-mediated 1C units
in proliferating cancer cells. Here, we show that under
physiological folate levels in the cell environment,
cytosolic serine-hydroxymethyltransferase (SHMT1) is the
predominant source of 1C units in a variety of cancers,
while mitochondrial 1C flux is overly repressed.
Tumor-specific reliance on cytosolic 1C flux is associated
with poor capacity to retain intracellular folates, which is
determined by the expression of SLC19A1, which encodes the
reduced folate carrier (RFC). We show that silencing SHMT1
in cells with low RFC expression impairs pyrimidine
biosynthesis and tumor growth in vivo. Overall, our
findings reveal major diversity in cancer cell utilization
of the cytosolic versus mitochondrial folate cycle across
tumors and SLC19A1 expression as a marker for increased
reliance on SHMT1.},
keywords = {SHMT (Other) / cancer metabolism (Other) / folate cycle
(Other) / in vivo (Other) / isotope tracing (Other) /
metabolomics (Other) / mitochondria (Other) / one-carbon
flux (Other) / physiologic medium (Other) / reduced folate
carrier (Other) / serine hydroxymethyltransferase (Other)},
cin = {B070},
ddc = {570},
cid = {I:(DE-He78)B070-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33326752},
doi = {10.1016/j.cmet.2020.12.002},
url = {https://inrepo02.dkfz.de/record/166539},
}