Polyamine Metabolism in Cancer Biology

Polyamines are small, positively charged molecules—principally putrescine, spermidine and spermine—that are vital for cell growth, gene expression and the maintenance of chromatin structure. In cancer, the tightly regulated balance of polyamine biosynthesis, catabolism and transport is frequently disrupted, leading to elevated intracellular concentrations that support hyperproliferation and survival. Key biosynthetic enzymes such as ornithine decarboxylase (ODC1) and S-adenosylmethionine decarboxylase drive the conversion of amino acid precursors into polyamines, while catabolic pathways and membrane transport systems adjust their intracellular levels. Oncogenic signals from MYC, RAS and mTOR pathways up-regulate polyamine synthesis and uptake, reinforcing protein translation, stabilising nucleic acids and modulating redox homeostasis. Dysregulated polyamine metabolism also reshapes the tumour microenvironment by influencing immune cell function and extracellular matrix remodelling. Therapeutic strategies target this metabolic vulnerability using enzyme inhibitors, transport blockers and combination approaches that can potentiate chemotherapy, prevent carcinogenesis and relieve tumour-induced immunosuppression.

Research from Nature Portfolio

One study in colorectal cancer has revealed that overexpression of spermine synthase collaborates with MYC-driven microRNAs to suppress the pro-apoptotic factor Bim. Genetic disruption of the synthase enzyme leads to spermidine accumulation, nuclear translocation of FOXO3a and Bim induction, triggering apoptosis. Combined inhibition of MYC activity and spermine synthase dramatically increases apoptosis and tumour regression in preclinical models, uncovering a convergent survival mechanism that may be exploited therapeutically.

Polyamine Metabolism in Cancer Biology publication trend

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

Technical terms

Polyamines: Small organic cations (putrescine, spermidine, spermine) involved in growth, gene regulation and chromatin compaction.

Ornithine Decarboxylase (ODC1): Rate-limiting enzyme converting ornithine to putrescine in polyamine biosynthesis.

Hypusination: Post-translational modification of EIF5A requiring spermidine, essential for translation elongation.

Hypusine: Unusual amino acid formed on EIF5A that is critical for its function in protein synthesis.

Xenograft: Transplantation of human cancer cells into immunodeficient mice for in vivo study.

Tumour Microenvironment: Network of stromal cells, immune infiltrate and extracellular matrix interacting with cancer cells.

Polyamine Blockade Therapy (PBT): Combined strategy inhibiting synthesis and uptake of polyamines to suppress tumour growth and relieve immunosuppression.

References

1. Polyamine and EIF5A hypusination downstream of c-Myc confers targeted therapy resistance in BRAF mutant melanoma. Molecular Cancer (2024).
2. Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis‐Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment. Advanced Science (2024).
3. Polyamine metabolism is a central determinant of helper T cell lineage fidelity. Cell (2021).
4. Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression. Nature Communications (2020).
5. Oil for the cancer engine: The cross-talk between oncogenic signaling and polyamine metabolism. Science Advances (2018).