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Cancer-associated fibroblast-derived urea cycle metabolites promote colorectal cancer growth

GSE285472 Homo sapiens Expression profiling by high throughput sequencing 5 samples Submitted 2025/01/31 Platform GPL23227
Summary
Urea cycle (UC) dysfunction is linked to both tumorigenesis and poor prognosis in multiple cancers. However, the role of UC metabolism in tumor-stroma crosstalk is unclear. Here, we show that colorectal cancer (CRC) cells induce reprogramming of UC metabolism in cancer-associated fibroblasts (CAFs), which is mediated by CRC-derived exosomes. Reprogrammed CAFs support CRC cell growth by providing UC metabolites, especially arginine (Arg). Consequently, Arg deprivation resulted in growth inhibition of CRC cells. Furthermore, we found that Arg deprivation increases CRC’s dependence on putrescine (Put) and upregulates the expression of the polyamine biosynthetic rate-limiting enzyme ornithine decarboxylase (ODC). Combined Arg deprivation and ODC inhibitor effectively restrains CRC cell growth. Our study illustrates the UC metabolic interaction between CAFs and CRC cells and demonstrates the potential therapeutic utility of Arg restriction and ODC blockade combination treatment for colorectal cancer.
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Direct links to NCBI, no account and no request form: the whole study as GSE285472_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 5 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1203894 and SRA study SRP554199. Searching any of these in the dataset finder brings you back here.

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