Nutritional Stress Induced by Tryptophan-Degrading Enzymes Results in ATF4-Dependent Reprogramming of the Amino Acid Transporter Profile in Tumor Cells.
basic_science · Level V
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- Record sourced from PubMed, PMID 27651314.
- Also identified by PMC identifier 5096689.
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Abstract
Tryptophan degradation is an immune escape strategy shared by many tumors. However, cancer cells' compensatory mechanisms remain unclear. We demonstrate here that a shortage of tryptophan caused by expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulted in ATF4-dependent upregulation of several amino acid transporters, including SLC1A5 and its truncated isoforms, which in turn enhanced tryptophan and glutamine uptake. Importantly, SLC1A5 failed to be upregulated in resting human T cells kept under low tryptophan conditions but was enhanced upon cognate antigen T-cell receptor engagement. Our results highlight key differences in the ability of tumor and T cells to adapt to tryptophan starvation and provide important insights into the poor prognosis of tumors coexpressing IDO and SLC1A5. Cancer Res; 76(21); 6193-204. ©2016 AACR.
Medical subject headings
- Activating Transcription Factor 4
- Amino Acid Transport System ASC
- Amino Acid Transport Systems
- Cellular Reprogramming
- Indoleamine-Pyrrole 2,3,-Dioxygenase
- Minor Histocompatibility Antigens
- Neoplasms
- Tryptophan