St8sia1, also known as GD3 synthase, is a ganglioside synthesis enzyme. It is involved in the synthesis of GD2, a ganglioside. Its activity is related to multiple signaling pathways, and it plays an important role in various biological processes, especially in cancer-related events [1,2,3,4,5,7]. Genetic models, such as gene knockout mouse models, are valuable for studying its function.

In neuroblastoma, a forced adrenergic-to-mesenchymal transition leads to down-regulation of St8sia1, reducing GD2 synthesis and conferring resistance to anti-GD2 antibody [1]. In triple-negative breast cancer (TNBC), the inhibition of St8sia1 sensitizes the cancer cells to chemotherapy by suppressing Wnt/β-catenin and FAK/Akt/mTOR signaling pathways [2]. In rectal adenocarcinoma, overexpression of St8sia1 inhibits tumor progression via TGF-β1 signaling and promotes the tumoricidal effects of CD8+ T cells [3]. In TNBC, St8sia1 regulates tumor growth and metastasis by activating the FAK-AKT-mTOR signaling pathway [4]. In bladder cancer, St8sia1 overexpression inhibits cell proliferation, migration, and invasion by blocking the JAK/STAT signaling pathway [5]. In gliomas, St8sia1-deficiency in mice alters the tumor environment, reducing disease severity [6].

In conclusion, St8sia1 is crucial in cancer-related biological processes. Gene knockout mouse models have revealed its role in various cancers, including neuroblastoma, TNBC, rectal adenocarcinoma, bladder cancer, and gliomas. Understanding St8sia1 provides insights into cancer mechanisms and potential therapeutic strategies.

References:

1. Mabe, Nathaniel W, Huang, Min, Dalton, Guillermo N, Stegmaier, Kimberly, Majzner, Robbie G. 2022. Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1. In Nature cancer, 3, 976-993. doi:10.1038/s43018-022-00405-x. https://pubmed.ncbi.nlm.nih.gov/35817829/

2. Wan, H, Li, Z, Wang, H, Cai, F, Wang, L. 2020. ST8SIA1 inhibition sensitizes triple negative breast cancer to chemotherapy via suppressing Wnt/β-catenin and FAK/Akt/mTOR. In Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 23, 902-910. doi:10.1007/s12094-020-02484-7. https://pubmed.ncbi.nlm.nih.gov/32939659/

3. Zhang, Chang, Wang, Yeli, Yu, Yao, Xiao, Xiao, Hao, Leilei. 2024. Overexpression of ST8Sia1 inhibits tumor progression by TGF-β1 signaling in rectal adenocarcinoma and promotes the tumoricidal effects of CD8+ T cells by granzyme B and perforin. In Annals of medicine, 57, 2439539. doi:10.1080/07853890.2024.2439539. https://pubmed.ncbi.nlm.nih.gov/39656552/

4. Nguyen, Khoa, Yan, Yuanqing, Yuan, Bin, Andreeff, Michael, Battula, V Lokesh. 2018. ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK-AKT-mTOR Signaling Pathway. In Molecular cancer therapeutics, 17, 2689-2701. doi:10.1158/1535-7163.MCT-18-0399. https://pubmed.ncbi.nlm.nih.gov/30237308/

5. Yu, Shengjin, Wang, Shidan, Sun, Xiaoxin, Yang, Deyong, Jiang, Yu. 2021. ST8SIA1 inhibits the proliferation, migration and invasion of bladder cancer cells by blocking the JAK/STAT signaling pathway. In Oncology letters, 22, 736. doi:10.3892/ol.2021.12997. https://pubmed.ncbi.nlm.nih.gov/34429775/

6. Zhang, Pu, Ohkawa, Yuki, Yamamoto, Satoko, Furukawa, Keiko, Furukawa, Koichi. . St8sia1-deficiency in mice alters tumor environments of gliomas, leading to reduced disease severity. In Nagoya journal of medical science, 83, 535-549. doi:10.18999/nagjms.83.3.535. https://pubmed.ncbi.nlm.nih.gov/34552288/

7. Hu, Xu, Yang, Yanfei, Wang, Yaohui, Ren, Shangqing, Li, Xiang. 2022. Identifying an Immune-Related Gene ST8SIA1 as a Novel Target in Patients With Clear-Cell Renal Cell Carcinoma. In Frontiers in pharmacology, 13, 901518. doi:10.3389/fphar.2022.901518. https://pubmed.ncbi.nlm.nih.gov/35873547/