Glycolytic Enzymes in Cancer Biology

Cancer cells frequently reprogram their metabolism to support rapid proliferation and survival under adverse conditions. Central to this reprogramming is enhanced glycolysis, often referred to as the Warburg effect, in which glucose is preferentially converted to lactate despite adequate oxygen supply. Glycolytic enzymes such as hexokinase, phosphofructokinase, pyruvate kinase and enolase not only catalyse key steps in glucose catabolism but also fulfil regulatory and “moonlighting” roles that influence gene expression, cell signalling and the tumour microenvironment. For example, pyruvate kinase M2 (PKM2) can translocate to the nucleus to modulate transcription, while enolase isoforms may localise to the cell surface to promote invasion. Altered expression or post-translational modification of these enzymes has been linked to cell cycle progression, resistance to apoptosis, motility and angiogenesis. Moreover, high glycolytic flux contributes to acidification of the extracellular milieu, which in turn shapes immune cell function and facilitates metastasis. The dual metabolic and non-metabolic functions of glycolytic enzymes render them attractive targets for novel diagnostics and combination therapies that aim to exploit tumour vulnerabilities while preserving normal tissue homeostasis.

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Glycolytic Enzymes in Cancer Biology publication trend

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

Technical terms

Glycolysis: A sequence of enzymatic reactions converting glucose to pyruvate, producing ATP and NADH. Warburg effect: The preference of cancer cells for aerobic glycolysis over oxidative phosphorylation. Pyruvate kinase M2 (PKM2): A glycolytic enzyme isoform that can shift between tetrameric metabolic and dimeric signalling states, influencing gene expression. Enolase: An enzyme catalysing the conversion of 2-phosphoglycerate to phosphoenolpyruvate; isoforms (ENO1, ENO2) have additional roles in invasion and immune modulation. Tumour microenvironment: The local cellular milieu of a tumour, including stromal cells, immune infiltrates, extracellular matrix and metabolites. Metabolic reprogramming: The alteration of cellular metabolic pathways to meet the biosynthetic and energetic demands of proliferating cancer cells.

References

1. Mediation of PKM2-dependent glycolytic and non-glycolytic pathways by ENO2 in head and neck cancer development. Journal of Experimental & Clinical Cancer Research (2023).
2. Single-cell and spatial transcriptomics reveal a high glycolysis B cell and tumor-associated macrophages cluster correlated with poor prognosis and exhausted immune microenvironment in diffuse large B-cell lymphoma. Biomarker Research (2024).
3. Modulating Glycolysis to Improve Cancer Therapy. International Journal of Molecular Sciences (2023).