Transketolase Function in Cancer Metabolism

Transketolase (TKT) occupies a central position in the non-oxidative branch of the pentose phosphate pathway (PPP), catalysing reversible transfers of two-carbon units between sugar phosphates. In cancer cells, TKT supports anabolic growth by supplying ribose-5-phosphate for nucleotide synthesis and by maintaining redox balance via NADPH generation. Beyond its canonical metabolic role, TKT can translocate to the nucleus, where it interacts with signalling kinases and transcriptional regulators to modulate cell proliferation and stress responses. Dysregulation of TKT expression, activity or localisation contributes to metastatic spread, therapeutic resistance and immune evasion across multiple tumour types. Recent work has revealed intricate post-translational control of TKT by phosphorylation, ubiquitination and PARylation, as well as transcriptional regulation by oncogenic factors, all of which converge on the rewiring of glucose metabolism to support uncontrolled growth.

Research from Nature Portfolio

Emerging insights into the cell‐cycle control of PPP flux have uncovered that the anaphase-promoting complex coupled to its adaptor CDH1 orchestrates the accumulation and subsequent degradation of a transketolase-like isoform (TKTL1). In late G1 and S phases, elevated TKTL1 levels form heterodimers with canonical transketolase to boost ribose-5-phosphate output, fuelling DNA synthesis. Following S-phase completion, APC/CCDH1 targets TKTL1 for proteasomal turnover, synchronising nucleotide supply with replication demands. In cancer cells, deregulated CDH1 or persistent TKTL1 overexpression leads to ribose-5-phosphate surpluses, accelerating DNA replication and cell‐cycle progression in a manner that is saturable by ribose availability. This work establishes a direct link between cell-cycle machinery and metabolic enzyme regulation, illuminating how dysregulated PPP control can drive tumour proliferation.

Transketolase Function in Cancer Metabolism publication trend

The graph below shows the total number of articles in transketolase function in cancer metabolism across all publications each year (not limited to Nature Index journals).

Technical terms

Transketolase (TKT): A thiamine-dependent enzyme in the non-oxidative pentose phosphate pathway that transfers two-carbon units between sugar phosphates.

Pentose phosphate pathway (PPP): A metabolic route branching from glycolysis that generates ribose-5-phosphate for nucleotide synthesis and NADPH for redox homeostasis.

Reactive oxygen species (ROS): Reactive molecules derived from oxygen that function as signalling mediators or cause oxidative damage at high concentrations.

Ubiquitination: Covalent attachment of ubiquitin to lysine residues on target proteins, often marking them for degradation by the proteasome or altering their activity.

PARylation: Post-translational addition of poly(ADP-ribose) chains by PARP enzymes, regulating DNA repair and protein interactions.

References

1. Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice. Experimental & Molecular Medicine (2023).
2. HMGA1 promotes the progression of esophageal squamous cell carcinoma by elevating TKT-mediated upregulation of pentose phosphate pathway. Cell Death & Disease (2024).
3. TKT-PARP1 axis induces radioresistance by promoting DNA double-strand break repair in hepatocellular carcinoma. Oncogene (2024).
4. APC/CCDH1 synchronizes ribose-5-phosphate levels and DNA synthesis to cell cycle progression. Nature Communications (2019).
5. Transketolase (TKT) activity and nuclear localization promote hepatocellular carcinoma in a metabolic and a non-metabolic manner. Journal of Experimental & Clinical Cancer Research (2019).