Colorectal cancer cell-derived exosomes induce metabolic reprogramming of cancer-associated fibroblasts to promote colorectal cancer growth
Year: 2025
Type: article
Abstract: Urea cycle (UC) dysfunction drives tumorigenesis and poor prognosis, yet its role in tumor-stroma crosstalk is unclear. Here we show that colorectal cancer (CRC) cells reprogram UC metabolism in cancer-associated fibroblasts (CAFs) via CRC-derived exosomes. Reprogrammed CAFs support CRC cell growth by providing UC metabolites, especially arginine (Arg). Depriving CRC cells of Arg halts their growth and simultaneously increases their reliance on putrescine while up-regulating ornithine decarboxylase (ODC), the polyamine-biosynthesis gatekeeper. 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.
Source: Discover Oncology
Authors: Guopeng Pan, Zexiong Cheng, Yiwei Wang, Changxi Wu, Fang Wang, Qing Li, Xiangyu Wang, Yuequan Zeng, Yuqin Li, Kai Li, Xi Lin, Fan Xing, Youwei Huang, Jun Liu, Rui Wang
Institutions: Jinan University, Southern Medical University, Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Gastrointestinal Disease Research Center, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Medical College, Southern Medical University Shenzhen Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,690
Awards: G1046523662, G6813634973, G7670541093
OpenAlex ID: W4416599444