Ggct-KO Mouse

Ggct, also known as γ -glutamylcyclotransferase, is an important enzyme in the glutathione metabolism pathway. Glutathione is crucial for maintaining cellular redox balance, and thus Ggct plays a significant role in various biological processes related to antioxidant defense [3,4,7].

In p53 -deficient osteosarcoma, Myc upregulates Ggct by binding to its promoter, and deletion of Ggct suppresses osteosarcomagenesis in mice, suggesting Ggct's role in promoting tumor development [2]. In mice, Ggct deletion leads to splenomegaly and progressive anaemia due to elevated oxidative damage and shortened lifespan of red blood cells, highlighting its importance in erythrocyte antioxidant defense and survival [3]. In multiple cancer types such as colorectal cancer, glioma, papillary thyroid cancer, and bladder urothelial cell carcinoma, high Ggct expression is associated with poor prognosis, and its knockdown inhibits cancer cell proliferation, migration, invasion, and in some cases, promotes ferroptosis [1,5,6,8,9,10].

In conclusion, Ggct is essential for maintaining cellular redox balance, especially in erythrocytes. Through gene knockout mouse models, it has been revealed that Ggct plays a role in promoting the development of certain cancers. These findings highlight Ggct as a potential therapeutic target in cancer treatment [2,3,1,5,6,8,9,10].

References:

1. Huang, Qi, Zhou, Yuanhang, Li, Yue, Liao, Zhiwei. 2020. GGCT promotes colorectal cancer migration and invasion via epithelial-mesenchymal transition. In Oncology letters, 20, 1063-1070. doi:10.3892/ol.2020.11692. https://pubmed.ncbi.nlm.nih.gov/32724344/

2. Ueno, Tomoya, Otani, Shohei, Date, Yuki, Nakata, Susumu, Ito, Kosei. 2024. Myc upregulates Ggct, γ-glutamylcyclotransferase to promote development of p53-deficient osteosarcoma. In Cancer science, 115, 2961-2971. doi:10.1111/cas.16255. https://pubmed.ncbi.nlm.nih.gov/38924236/

3. He, Zaoke, Sun, Xiaoqin, Wang, Shixiang, Hao, Piliang, Liu, Xue-Song. 2021. Ggct (γ-glutamyl cyclotransferase) plays an important role in erythrocyte antioxidant defense and red blood cell survival. In British journal of haematology, 195, 267-275. doi:10.1111/bjh.17775. https://pubmed.ncbi.nlm.nih.gov/34409610/

4. He, Zaoke, Wang, Shixiang, Shao, Yuanyuan, Zhang, Feng, Liu, Xue-Song. 2019. Ras Downstream Effector GGCT Alleviates Oncogenic Stress. In iScience, 19, 256-266. doi:10.1016/j.isci.2019.07.036. https://pubmed.ncbi.nlm.nih.gov/31400748/

5. Shen, Shang-Hang, Chen, Si-Fang, Guo, Jian-Feng, Wang, Zhan-Xiang. 2024. The GGCT and REST positive feedback loop promotes tumor growth in Glioma. In Translational oncology, 49, 102083. doi:10.1016/j.tranon.2024.102083. https://pubmed.ncbi.nlm.nih.gov/39128259/

6. Li, Han-Ning, Zhang, Hui-Min, Li, Xing-Rui, Liao, Xing-Hua, Du, Ya-Ying. . MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44. In Endocrinology, 163, . doi:10.1210/endocr/bqac022. https://pubmed.ncbi.nlm.nih.gov/35213720/

7. Kageyama, Susumu, Ii, Hiromi, Taniguchi, Keiko, Kawauchi, Akihiro, Nakata, Susumu. 2018. Mechanisms of Tumor Growth Inhibition by Depletion of γ-Glutamylcyclotransferase (GGCT): A Novel Molecular Target for Anticancer Therapy. In International journal of molecular sciences, 19, . doi:10.3390/ijms19072054. https://pubmed.ncbi.nlm.nih.gov/30011933/

8. Zhang, Hui-Min, Li, Han-Ning, Qi, Enbo, Yang, Zhi-Fang, Liao, Xing-Hua. 2025. GGCT Inhibits Ferroptosis in PTC Cells by Upregulating p53 Through RPS15A. In Cancer science, , . doi:10.1111/cas.70039. https://pubmed.ncbi.nlm.nih.gov/40044122/

9. Zhang, Hui-Min, Li, Zi-Yi, Dai, Zhou-Tong, Zhang, Tong-Cun, Liao, Xing-Hua. 2022. Interaction of MRPL9 and GGCT Promotes Cell Proliferation and Migration by Activating the MAPK/ERK Pathway in Papillary Thyroid Cancer. In International journal of molecular sciences, 23, . doi:10.3390/ijms231911989. https://pubmed.ncbi.nlm.nih.gov/36233293/

10. Guo, Y S, Wu, Y D, Ma, H, Zhang, S D, Zang, Y J. . [The expression of GGCT in the bladder urothelial cell carcinoma and its clinical significance]. In Zhonghua zhong liu za zhi [Chinese journal of oncology], 43, 1183-1187. doi:10.3760/cma.j.cn112152-20200326-00264. https://pubmed.ncbi.nlm.nih.gov/34794221/