| First Author | Newman AC | Year | 2021 |
| Journal | Mol Cell | Volume | 81 |
| Issue | 11 | Pages | 2290-2302.e7 |
| PubMed ID | 33831358 | Mgi Jnum | J:307146 |
| Mgi Id | MGI:6718904 | Doi | 10.1016/j.molcel.2021.03.019 |
| Citation | Newman AC, et al. (2021) Immune-regulated IDO1-dependent tryptophan metabolism is source of one-carbon units for pancreatic cancer and stellate cells. Mol Cell 81(11):2290-2302.e7 |
| abstractText | Cancer cells adapt their metabolism to support elevated energetic and anabolic demands of proliferation. Folate-dependent one-carbon metabolism is a critical metabolic process underpinning cellular proliferation supplying carbons for the synthesis of nucleotides incorporated into DNA and RNA. Recent research has focused on the nutrients that supply one-carbons to the folate cycle, particularly serine. Tryptophan is a theoretical source of one-carbon units through metabolism by IDO1, an enzyme intensively investigated in the context of tumor immune evasion. Using in vitro and in vivo pancreatic cancer models, we show that IDO1 expression is highly context dependent, influenced by attachment-independent growth and the canonical activator IFNgamma. In IDO1-expressing cancer cells, tryptophan is a bona fide one-carbon donor for purine nucleotide synthesis in vitro and in vivo. Furthermore, we show that cancer cells release tryptophan-derived formate, which can be used by pancreatic stellate cells to support purine nucleotide synthesis. |
