Immune-regulated IDO1-dependent tryptophan metabolism is source of one-carbon units for pancreatic cancer and stellate cells DOI Creative Commons
Alice C. Newman, Mattia Falcone, Alejandro Huerta Uribe

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(11), P. 2290 - 2302.e7

Published: April 7, 2021

Cancer cells adapt their metabolism to support elevated energetic and anabolic demands of proliferation. Folate-dependent one-carbon is a critical metabolic process underpinning cellular proliferation supplying carbons for the synthesis nucleotides incorporated into DNA RNA. Recent research has focused on nutrients that supply one-carbons folate cycle, particularly serine. Tryptophan theoretical source units through by IDO1, an enzyme intensively investigated in context tumor immune evasion. Using vitro vivo pancreatic cancer models, we show IDO1 expression highly dependent, influenced attachment-independent growth canonical activator IFNγ. In IDO1-expressing cells, tryptophan bona fide donor purine nucleotide vivo. Furthermore, release tryptophan-derived formate, which can be used stellate synthesis.

Language: Английский

Serine enrichment in tumors promotes regulatory T cell accumulation through sphinganine-mediated regulation of c-Fos DOI
Sicong Ma, Roger Sandhoff,

Xiu Luo

et al.

Science Immunology, Journal Year: 2024, Volume and Issue: 9(94)

Published: April 19, 2024

CD4 + regulatory T (T reg ) cells accumulate in the tumor microenvironment (TME) and suppress immune system. Whether how metabolite availability TME influences cell differentiation is not understood. Here, we measured 630 metabolites found that serine palmitic acid, substrates required for synthesis of sphingolipids, were enriched. A serine-free diet or a deficiency Sptlc2, rate-limiting enzyme catalyzing sphingolipid synthesis, suppressed accumulation inhibited growth. Sphinganine, an intermediate physically interacted with transcription factor c-Fos. Sphinganine c-Fos interactions enhanced genome-wide recruitment to regions near start sites target genes including Pdcd1 (encoding PD-1), which promoted increased inducible vitro PD-1–dependent manner. Thus, Sptlc2-mediated translates extracellular information into nuclear signals limits antitumor immunity.

Language: Английский

Citations

18
NIR-II imaging-guided precise photodynamic therapy for augmenting tumor-starvation therapy by glucose metabolism reprogramming interference DOI
Xiawei Wu, Yong Fan, Kairuo Wang

et al.

Science Bulletin, Journal Year: 2024, Volume and Issue: 69(9), P. 1263 - 1274

Published: Feb. 9, 2024

Language: Английский

Citations

17
Metabolic Reprogramming in Anticancer Drug Resistance: A Focus on Amino Acids DOI
Erica Pranzini, Elisa Pardella, Paolo Paoli

et al.

Trends in cancer, Journal Year: 2021, Volume and Issue: 7(8), P. 682 - 699

Published: March 19, 2021

Language: Английский

Citations

88
Structural insights into the regulation of human serine palmitoyltransferase complexes DOI

Yingdi Wang,

Yiming Niu, Zhe Zhang

et al.

Nature Structural & Molecular Biology, Journal Year: 2021, Volume and Issue: 28(3), P. 240 - 248

Published: Feb. 8, 2021

Language: Английский

Citations

83
Immune-regulated IDO1-dependent tryptophan metabolism is source of one-carbon units for pancreatic cancer and stellate cells DOI Creative Commons
Alice C. Newman, Mattia Falcone, Alejandro Huerta Uribe

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(11), P. 2290 - 2302.e7

Published: April 7, 2021

Cancer cells adapt their metabolism to support elevated energetic and anabolic demands of proliferation. Folate-dependent one-carbon is a critical metabolic process underpinning cellular proliferation supplying carbons for the synthesis nucleotides incorporated into DNA RNA. Recent research has focused on nutrients that supply one-carbons folate cycle, particularly serine. Tryptophan theoretical source units through by IDO1, an enzyme intensively investigated in context tumor immune evasion. Using vitro vivo pancreatic cancer models, we show IDO1 expression highly dependent, influenced attachment-independent growth canonical activator IFNγ. In IDO1-expressing cells, tryptophan bona fide donor purine nucleotide vivo. Furthermore, release tryptophan-derived formate, which can be used stellate synthesis.

Language: Английский

Citations

75