# ODC1 Polyamine Metabolism Drives Prostate Cancer via AKT and Splicing

## TL;DR

This study shows that ODC1, a key enzyme in polyamine metabolism, promotes prostate cancer by affecting gene expression and splicing, especially through the AKT pathway.

## Contribution

The study reveals a novel mechanistic link between ODC1 activity, splicing regulation, and prostate cancer progression via the AKT pathway.

## Key findings

- Reducing ODC1 expression slowed prostate cancer cell growth, movement, and increased cell death.
- Over 1,000 differentially expressed genes and 2,000 alternative splicing events were linked to cancer-related pathways.
- Genes like CAV1 and ITGB1 connected ODC1 activity to the AKT signaling pathway in prostate cancer progression.

## Abstract

Prostate cancer is an aggressive disease with limited quantifiable biomarkers. One gene of interest is ODC1, which encodes ornithine decarboxylase, the rate‐limiting enzyme converting ornithine to putrescine in polyamine metabolism. Although ODC1 is known to be involved in prostate cancer development, exactly how it drives the disease mechanistically is not fully understood. To explore this, we created a prostate cancer cell model with reduced ODC1 expression and examined its effects on tumour behaviours. Knocking down ODC1 significantly slowed cell growth and movement while increasing cell death. Using RNA sequencing, we identified over one thousand differentially expressed genes, with 565 upregulated and 497 downregulated, primarily linked to angiogenesis and cell adhesion. We also found more than two thousand alternative splicing events connected to cell cycle regulation and protein modification. Notably, genes including CAV1, ITGB1, BNIP3, and YTHDF2 were associated with the AKT signalling pathway, suggesting a functional link between ODC1 activity and cancer progression. These results indicate that ODC1 influences prostate cancer cell behaviour by regulating both gene expression and splicing, particularly affecting pathways involved in angiogenesis, adhesion, and the cell cycle. This points to the AKT pathway and polyamine metabolism as potentially valuable targets for future prostate cancer therapies.