Odc1, or ornithine decarboxylase 1, is a rate-limiting enzyme in polyamine biosynthesis, metabolizing l-ornithine to polyamines. Polyamines are involved in multiple biological processes such as cell differentiation, proliferation, and migration [4]. Odc1 has been linked to pathways like WNT/MYC and AKT/GSK3β/β-catenin, and is of great biological importance in various physiological and pathological conditions [2,5]. Genetic models, especially KO/CKO mouse models, can be valuable for studying its functions.

In osteoclast differentiation, loss of Nrf2 or iron supplementation upregulates Odc1, which decreases ornithine levels and promotes osteoclast differentiation, uncovering a novel Nrf2-iron-ornithine metabolic axis [1]. In neuroblastoma, knockdown of Odc1 significantly attenuated the promotion effect of CDC27 on cell proliferation, metastasis, and sphere-formation ability, and reversed CDC27-induced pro-ferroptotic effect, indicating that the CDC27/ODC1 axis promotes tumorigenesis and acts as a positive regulator of ferroptosis in NB [3]. In macrophages, ODC1 overexpression inhibited the phosphorylation of multiple transcription factors, attenuated the inflammatory response, and inhibited reactive oxygen species-induced and caspase-dependent apoptosis, suggesting it as a potential therapeutic target for inflammatory diseases [4]. In hepatocellular carcinoma (HCC), a decrease in Odc1 expression inhibits HCC cell proliferation, migration, invasion, and induces cell cycle arrest both in vitro and in vivo, and Odc1 promotes HCC cell progression via the AKT/GSK3β/β-catenin pathway and modulation of the acidotic microenvironment [5].

In conclusion, Odc1 plays crucial roles in multiple biological processes including cell proliferation, differentiation, and inflammatory response. Through model-based research, especially KO/CKO mouse models, its roles in diseases such as osteoporosis, neuroblastoma, inflammatory diseases, and hepatocellular carcinoma have been revealed, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Dong, Yimin, Kang, Honglei, Peng, Renpeng, Li, Feng, Song, Kehan. 2024. A clinical-stage Nrf2 activator suppresses osteoclast differentiation via the iron-ornithine axis. In Cell metabolism, 36, 1679-1695.e6. doi:10.1016/j.cmet.2024.03.005. https://pubmed.ncbi.nlm.nih.gov/38569557/

2. Bi, Guoshu, Liang, Jiaqi, Bian, Yunyi, Gan, Boyi, Zhan, Cheng. 2024. Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer. In Nature communications, 15, 2461. doi:10.1038/s41467-024-46776-w. https://pubmed.ncbi.nlm.nih.gov/38504107/

3. Qiu, Lin, Zhou, Rui, Luo, Ziyan, Wu, Jiangxue, Jiang, Hua. 2022. CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma. In Frontiers in oncology, 12, 774458. doi:10.3389/fonc.2022.774458. https://pubmed.ncbi.nlm.nih.gov/35242701/

4. Jiang, Fang, Gao, Yue, Dong, Chunsheng, Xiong, Sidong. 2018. ODC1 inhibits the inflammatory response and ROS-induced apoptosis in macrophages. In Biochemical and biophysical research communications, 504, 734-741. doi:10.1016/j.bbrc.2018.09.023. https://pubmed.ncbi.nlm.nih.gov/30217446/

5. Ye, Zi, Zeng, Zhirui, Shen, Yiyi, Chen, Zubing, Shen, Shiqiang. 2019. ODC1 promotes proliferation and mobility via the AKT/GSK3β/β-catenin pathway and modulation of acidotic microenvironment in human hepatocellular carcinoma. In OncoTargets and therapy, 12, 4081-4092. doi:10.2147/OTT.S198341. https://pubmed.ncbi.nlm.nih.gov/31239700/