The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Arginine reprograms metabolism in liver cancer via RBM39
Open accessAbstract
Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic reprogramming and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels are elevated in murine and patient hepatocellular carcinoma (HCC), despite reduced expression of arginine synthesis genes. Tumor cells accumulate high levels of arginine due to increased uptake and reduced arginine-to-polyamine conversion. Importantly, the high levels of arginine promote tumor formation via further metabolic reprogramming, including changes in glucose, amino acid, nucleotide, and fatty acid metabolism. Mechanistically, arginine binds RNA-binding motif protein 39 (RBM39) to control expression of metabolic genes. RBM39-mediated upregulation of asparagine synthesis leads to enhanced arginine uptake, creating a positive feedback loop to sustain high arginine levels and oncogenic metabolism. Thus, arginine is a second messenger-like molecule that reprograms metabolism to promote tumor growth.
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Cites
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Lin, J., Rao, D., Zhang, M., & Gao, Q. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01527-8 · Cited by 251
“Targeting RBM39 instead of circulating arginine may offer a way to reverse the oncogenic pathway triggered by high arginine pools in HCC cells, thereby avoiding the adverse side effects of circulating arginine-depleting therapy [63].”
BackgroundMolecular mechanisms in liver repair and regeneration: from physiology to therapeutics
Ma, X., Huang, T., Chen, X., Li, Q., Liao, M., Fu, L., Huang, J., Yuan, K., Wang, Z., & Zeng, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02104-8 · Cited by 133
The metabolic dialogue between intratumoural microbes and cancer: implications for immunotherapy
Situ, Y., Zhang, P., Zhang, C., Jiang, A., Zhang, N., Zhu, L., Mou, W., Liu, Z., Wong, H. Z. H., Zhang, J., et al. (2025) · eBioMedicine · doi:10.1016/j.ebiom.2025.105708 · Cited by 45
Metabolic reprogramming: The driving force behind cancer drug resistance
El-Sehrawy, A. A. M. A., Hsu, C.-Y., Alkhathami, A. G., Chandra, M., Basunduwah, T. S., Malathi, H., Senapati, J. N., Gautam, A., Kadhem, M., & Yasin, H. A. (2025) · Seminars in Oncology · doi:10.1016/j.seminoncol.2025.152392 · Cited by 11
Metadata
- Authors
- Mossmann, D., Müller, C., Park, S., Ryback, B., Colombi, M., Ritter, N., Weißenberger, D., Dazert, E., Coto-Llerena, M., Nuciforo, S., Blukacz, L., Ercan, C., Jimenez, V., Piscuoglio, S., Bosch, F., Terracciano, L. M., Sauer, U., Heim, M. H., & Hall, M. N.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 186
- Issue
- 23
- Pages
- 5068-5083.e23
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W4387408542
- Cited by
- 293
- References
- 71
- FWCI
- 23.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Mossmann, D., Müller, C., Park, S., Ryback, B., Colombi, M., Ritter, N., Weißenberger, D., Dazert, E., Coto-Llerena, M., Nuciforo, S., Blukacz, L., Ercan, C., Jimenez, V., Piscuoglio, S., Bosch, F., Terracciano, L. M., Sauer, U., Heim, M. H., & Hall, M. N. (2023). Arginine reprograms metabolism in liver cancer via RBM39. Cell. https://doi.org/10.1016/j.cell.2023.09.011
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
