A new scientific study identified taurine, which is made naturally in the body and consumed through some foods, as a key regulator of myeloid cancers such as leukemia, according to a paper published in the journal Nature. The Wilmot Cancer Institute investigators at the University of Rochester were able to block the growth of leukemia in mouse models and in human leukemia cell samples by preventing taurine from entering cancer cells. The research team discovered that taurine is produced by a subset of normal cells in the bone marrow microenvironment, the tissue inside bones where myeloid cancers begin and expand. Leukemia cells are unable to make taurine themselves, so they rely on a taurine transporter (encoded by the SLC6A6 gene) to grab taurine from the bone marrow environment and transported inside them.
The discovery occurred as scientists were mapping what happens within the bone marrow and its ecosystem-a longtime focus among Wilmot researchers, who have advanced the science around the microenvironment with the goal of improving blood cancer treatments. Researchers also discovered that as leukemia cells drink up taurine, it promotes cellular glycolysis (glucose metabolism to produce energy) to feed cancer growth. Prior to this, it was not known that taurine might have a cancer-promoting role. Leukemia has several subtypes and survival rates vary. This study finds that taurine transporter expression is essential for the growth of multiple subtypes including acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS), which all originate from stem cells in the bone marrow.
SLC6A6 encodes taurine transporter (TAUT), which has high affinity for the non-essential amino acid taurine, and low affinity for β-alanine. The team experiments indicate that Slc6a6 expression can be directly induced by oncogenes. While the leukaemia microenvironment did not express enzymes required for β-alanine synthesis (Gadl1 and Cndp1), those needed for taurine biosynthesis (Cdo1 and Csad) were expressed in bone cells. To determine whether small-molecule inhibitors of TAUT can effectively block leukaemia growth, we used two well-characterized structural taurine analogues that inhibit uptake: TAG and GES. Importantly, while they impaired growth of primary human AML cells in colony assays by 1.8- to 20-fold, they did not impact normal human CD34+ regular stem cell colony growth.
As TAG and GES did not effectively block taurine uptake in vivo, scinetists used shRNA-based approaches to determine the impact of inhibiting TAUT expression on human AML growth. Knocking down SLC6A6 expression using two independent shRNAs significantly impaired taurine uptake by 2.2 to 3.4-fold, as well as the colony-forming ability of human CML, AML and MDS cell lines by 2- to 12-fold. Metabolomic analysis of mouse LSCs identified significant downregulation of glycolysis-related pathways and metabolites such as pyruvate, glyceraldehyde-3-phosphate and 3-phosphoglycerate in Slc6a6−/− cells, suggesting that taurine may regulate energy metabolism. The team also identified the mTOR and c-Myc-dependent signaling beneath the ability of taurine to enhance glucose utrilization by leukemia cells.
mTOR is known to enhance glycolysis-related genes and taurine loss decrease mTOR complex phosphorylation and protein syntesis dependent on phospho-Rsk1 and phospho-eIF4B. Aminoacid sensing may activate mTOR with the help of the cellular sensor Rag-A (like it happens for leucine and other branched aminoacids). Scientists had a good intuition in hypothizing a similar mechanism and succeeded: taurine supplementation enhances the interaction of Rag-A with mTOR complex and subsequent lysosome anchoring to promote protein synthesis and to suppress any autophagic attempt. In light of early clinical success of glutamine inhibitors in MDS and AML, scientists deem that their research suggests that evaluating taurine-transport inhibitors in normal and leukaemic cells may be of therapeutic interest.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Sharma S et al. Nature 2025 May 14; in press.
Cao T et al. Cell. 2024 Apr 25; 187(9):2288-2304.
DiNardo CD et al. Nat Cancer 2024; 5:1515-1533.
