Glt8d1-KO Mouse

GLT8D1, or glycosyltransferase 8 domain containing 1, is located in the Golgi apparatus and is a UDP-dependent galactosyltransferase [6]. It is associated with transferase activity, catalyzing the formation of glycosidic bonds, which likely play important roles in various biological processes [6]. Its potential involvement in multiple pathways related to cell growth, migration, and tumorigenesis makes it a gene of interest in biological research, and genetic models could be valuable for further study.

In glioma, hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. Depletion of GLT8D1 inhibits self-renewal of glioma stem cells in vitro and represses tumor growth in glioma mouse models, also promoting cell cycle arrest at G2/M phase and cellular apoptosis [1]. In glioblastoma, higher GLT8D1 expression was observed compared to normal brain tissue, and increased in vitro expression enhanced the migration of GBM cell lines. Point mutations in the predicted active site reduced its glycosyltransferase activity and impaired GBM tumor cell migration [5]. In cutaneous melanoma, GLT8D1 overexpression was associated with poor overall survival, and in gastric cancer, high GLT8D1 expression was correlated with poor prognosis for patients [3,4]. However, in Chinese and Australian ALS patients, no significant association between GLT8D1 and ALS was found through various genetic analyses [2,7,8,9].

In conclusion, GLT8D1 plays crucial roles in the progression of certain cancers such as glioma, glioblastoma, cutaneous melanoma, and gastric cancer, mainly through influencing cell growth, migration, and survival. The lack of association with ALS in the studied cohorts suggests its limited role in this neurodegenerative disease. The use of gene knockout or knockdown models in cancer research has revealed GLT8D1's functions in tumor-related biological processes, providing potential therapeutic targets for these malignancies.

References:

1. Liu, Kun, Jiang, Liping, Shi, Yulin, Yang, Cuiping, Chen, Yongbin. 2022. Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. In Cell death and differentiation, 29, 1834-1849. doi:10.1038/s41418-022-00969-2. https://pubmed.ncbi.nlm.nih.gov/35301431/

2. Yilihamu, Mubalake, He, Ji, Liu, Xiangyi, Tian, Jinzhou, Fan, Dongsheng. 2021. GLT8D1 may not be significant in Chinese sporadic amyotrophic lateral sclerosis patients. In Neurobiology of aging, 102, 224.e1-224.e3. doi:10.1016/j.neurobiolaging.2021.01.028. https://pubmed.ncbi.nlm.nih.gov/33714647/

3. Hu, Hongyan, Li, Zhen, Zhou, Yongchun, Huang, Yunchao, Song, Xin. . GLT8D1 overexpression as a novel prognostic biomarker in human cutaneous melanoma. In Melanoma research, 29, 612-620. doi:10.1097/CMR.0000000000000631. https://pubmed.ncbi.nlm.nih.gov/31305325/

4. Xu, Huimei, Huang, Ke, Lin, Yimin, Ma, Xueni, Zhang, Dekui. 2023. Glycosyltransferase GLT8D1 and GLT8D2 serve as potential prognostic biomarkers correlated with Tumor Immunity in Gastric Cancer. In BMC medical genomics, 16, 123. doi:10.1186/s12920-023-01559-y. https://pubmed.ncbi.nlm.nih.gov/37277853/

5. Ilina, Elena I, Cialini, Camille, Gerloff, Dietlind L, Müller, Tanja, Mittelbronn, Michel. 2022. Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration. In iScience, 25, 103842. doi:10.1016/j.isci.2022.103842. https://pubmed.ncbi.nlm.nih.gov/35198895/

6. Vicente, João B, Guerreiro, Ana Catarina L, Felgueiras, Beatriz, Moremen, Kelley W, Costa, Júlia. 2023. Glycosyltransferase 8 domain-containing protein 1 (GLT8D1) is a UDP-dependent galactosyltransferase. In Scientific reports, 13, 21684. doi:10.1038/s41598-023-48605-4. https://pubmed.ncbi.nlm.nih.gov/38066107/

7. Chan Moi Fat, Sandrine, McCann, Emily P, Williams, Kelly L, Fifita, Jennifer A, Blair, Ian P. 2021. Genetic analysis of GLT8D1 and ARPP21 in Australian familial and sporadic amyotrophic lateral sclerosis. In Neurobiology of aging, 101, 297.e9-297.e11. doi:10.1016/j.neurobiolaging.2021.01.005. https://pubmed.ncbi.nlm.nih.gov/33581934/

8. Li, Wanzhen, Liu, Zhen, Sun, Weining, Tang, Beisha, Wang, Junling. 2019. Mutation analysis of GLT8D1 and ARPP21 genes in amyotrophic lateral sclerosis patients from mainland China. In Neurobiology of aging, 85, 156.e1-156.e4. doi:10.1016/j.neurobiolaging.2019.09.013. https://pubmed.ncbi.nlm.nih.gov/31653410/

9. Cao, Bei, Gu, Xiaojing, Wei, Qianqian, Chen, Xueping, Shang, Huifang. 2020. Mutation screening and burden analysis of GLT8D1 in Chinese patients with amyotrophic lateral sclerosis. In Neurobiology of aging, 101, 298.e17-298.e21. doi:10.1016/j.neurobiolaging.2020.10.017. https://pubmed.ncbi.nlm.nih.gov/33581933/