STK33, a serine/threonine kinase, participates in multiple biological processes. It is involved in signaling pathways such as those related to cell proliferation, apoptosis, and sperm development. In cancers, it has been associated with tumorigenesis and drug resistance, while in spermatogenesis, it is crucial for sperm flagella assembly [1,3,4,5,6,7,8].

In spermatogenesis, loss-of-function mutations of STK33 in humans and Stk33-/KI male mice led to male infertility due to abnormal sperm with defects in multiple structures like the mitochondrial sheath, fibrous sheath, outer dense fiber, and axoneme [1]. STK33 phosphorylates fibrous sheath components AKAP3 and AKAP4, regulating sperm flagella assembly [1]. In cancer research, STK33 knockout mouse models demonstrated its role in liver tumorigenesis, with STK33KO(flox/flox, Alb-ERT2-Cre) mice showing a lower incidence of tumour formation [4]. In addition, knockdown of STK33 in various cancer cell lines affected cell proliferation, migration, invasion, apoptosis, and autophagy, revealing its importance in cancer-related processes [3,5,6].

In conclusion, STK33 is essential for spermatogenesis and plays significant roles in cancer-related processes. The use of gene knockout mouse models, such as in male infertility and liver cancer studies, has provided valuable insights into the function of STK33 in these disease areas, highlighting its potential as a therapeutic target for male contraception and cancer treatment [1,2,4].

References:

1. Yu, Weiling, Li, Yang, Chen, Hong, Hu, Zhibin, Guo, Xuejiang. 2023. STK33 Phosphorylates Fibrous Sheath Protein AKAP3/4 to Regulate Sperm Flagella Assembly in Spermiogenesis. In Molecular & cellular proteomics : MCP, 22, 100564. doi:10.1016/j.mcpro.2023.100564. https://pubmed.ncbi.nlm.nih.gov/37146716/

2. Ku, Angela F, Sharma, Kiran L, Ta, Hai Minh, Kim, Choel, Matzuk, Martin M. 2024. Reversible male contraception by targeted inhibition of serine/threonine kinase 33. In Science (New York, N.Y.), 384, 885-890. doi:10.1126/science.adl2688. https://pubmed.ncbi.nlm.nih.gov/38781365/

3. Zhang, Shengjun, Wu, Haoyu, Wang, Kaiyu, Liu, Minli. 2019. STK33/ERK2 signal pathway contribute the tumorigenesis of colorectal cancer HCT15 cells. In Bioscience reports, 39, . doi:10.1042/BSR20182351. https://pubmed.ncbi.nlm.nih.gov/30760631/

4. Yang, Tian, Song, Bin, Zhang, Jin, Lu, Jun-Hua, Shen, Feng. 2014. STK33 promotes hepatocellular carcinoma through binding to c-Myc. In Gut, 65, 124-33. doi:10.1136/gutjnl-2014-307545. https://pubmed.ncbi.nlm.nih.gov/25398772/

5. Li, Xiaomei, Lin, Min, Liu, Min, Ye, Hong, Qin, Shuming. 2023. Interaction between STK33 and autophagy promoted renal cell carcinoma metastasis by regulating mTOR/ULK1 signaling pathway. In Molecular biology reports, 50, 5059-5067. doi:10.1007/s11033-023-08396-3. https://pubmed.ncbi.nlm.nih.gov/37101009/

6. Zhou, Bo, Xiang, Jie, Zhan, Canyang, Liu, Jianhua, Yan, Sheng. 2019. STK33 Promotes the Growth and Progression of Human Pancreatic Neuroendocrine Tumour via Activation of the PI3K/AKT/mTOR Pathway. In Neuroendocrinology, 110, 307-320. doi:10.1159/000501829. https://pubmed.ncbi.nlm.nih.gov/31261148/

7. Yoo, Dongkwan, Wu, Sichen, Choi, Seunghyuk, Huh, Sung-Oh, Sadra, Ali. 2024. STK33 as the functional substrate of miR-454-3p for suppression and apoptosis in neuroblastoma. In Molecules and cells, 47, 100145. doi:10.1016/j.mocell.2024.100145. https://pubmed.ncbi.nlm.nih.gov/39515612/

8. Feng, Lili, Xu, Xiaofang, Zhao, Keke. 2021. NFYB potentiates STK33 activation to promote cisplatin resistance in diffuse large B-cell lymphoma. In Leukemia research, 111, 106708. doi:10.1016/j.leukres.2021.106708. https://pubmed.ncbi.nlm.nih.gov/34536775/