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000166539 0247_ $$2doi$$a10.1016/j.cmet.2020.12.002
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000166539 037__ $$aDKFZ-2020-02982
000166539 041__ $$aeng
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000166539 1001_ $$aLee, Won Dong$$b0
000166539 245__ $$aTumor Reliance on Cytosolic versus Mitochondrial One-Carbon Flux Depends on Folate Availability.
000166539 260__ $$aCambridge, Mass.$$bCell Press$$c2021
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000166539 500__ $$a2021 Jan 5;33(1):190-198.e6 / #DKFZ-MOST-Ca173#
000166539 520__ $$aFolate 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.
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000166539 650_7 $$2Other$$aSHMT
000166539 650_7 $$2Other$$acancer metabolism
000166539 650_7 $$2Other$$afolate cycle
000166539 650_7 $$2Other$$ain vivo
000166539 650_7 $$2Other$$aisotope tracing
000166539 650_7 $$2Other$$ametabolomics
000166539 650_7 $$2Other$$amitochondria
000166539 650_7 $$2Other$$aone-carbon flux
000166539 650_7 $$2Other$$aphysiologic medium
000166539 650_7 $$2Other$$areduced folate carrier
000166539 650_7 $$2Other$$aserine hydroxymethyltransferase
000166539 7001_ $$0P:(DE-He78)5b40dbc49d2c1161db6578db740304e4$$aPirona, Anna Chiara$$b1
000166539 7001_ $$aSarvin, Boris$$b2
000166539 7001_ $$aStern, Alon$$b3
000166539 7001_ $$aNevo-Dinur, Keren$$b4
000166539 7001_ $$aBesser, Elazar$$b5
000166539 7001_ $$aSarvin, Nikita$$b6
000166539 7001_ $$aLagziel, Shoval$$b7
000166539 7001_ $$aMukha, Dzmitry$$b8
000166539 7001_ $$aRaz, Shachar$$b9
000166539 7001_ $$aAizenshtein, Elina$$b10
000166539 7001_ $$aShlomi, Tomer$$b11
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000166539 9141_ $$y2021
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