Styk1, also known as serine/threonine/tyrosine kinase 1 and NOK, is a receptor protein-tyrosine kinase-like molecule. It plays crucial roles in multiple biological processes, with its expression detected in several human organs. Styk1 is involved in pathways related to cell cycle, autophagy, and migration, and is of great importance in tumorigenesis and metastasis in various cancers [1-8]. Genetic models, such as gene-knockout mouse models, have been instrumental in studying its functions.

In gene-knockout studies, Styk1-deleted mice were generated using Nuclease technology technology. Surprisingly, deletion of Styk1 promoted tumor progression in multiple tumor models, including NK-cell-specific target cell clearance, subcutaneous and intravenous injection of B16F10 melanoma, and the spontaneous breast cancer model MMTV-PyMT. This was accompanied by a reduction of NK cell accumulation in tumor tissues. RNA-seq analysis revealed disparities in migration-and adhesion-related signaling pathways in Styk1-deficient NK cells, with a significant reduction in CCR2 expression. Also, over-expression of Styk1 in cell lines led to mitotic arrest and cytokinesis defects, and depletion of APC3 caused accumulation of Styk1 and G2/M arrest [1,2].

In conclusion, Styk1 plays a key role in mediating NK cell anti-tumor response through regulating CCR2 and trafficking. It also affects cell cycle late mitosis. The study of Styk1-KO mouse models has provided valuable insights into its functions in tumor progression, highlighting its potential as a target for cancer treatment [1,2].

References:

1. He, Junming, He, Yuexi, Biao, Ruojia, Dong, Zhongjun, Du, Juan. 2024. STYK1 mediates NK cell anti-tumor response through regulating CCR2 and trafficking. In Journal of translational medicine, 22, 943. doi:10.1186/s12967-024-05718-2. https://pubmed.ncbi.nlm.nih.gov/39415235/

2. Zeng, Su-Lin, Patel, Suraj S, Lv, Mo-Qi, Shen, Wen H, Liu, Li. 2022. STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1. In Heliyon, 8, e12058. doi:10.1016/j.heliyon.2022.e12058. https://pubmed.ncbi.nlm.nih.gov/36506394/