丝氨酸/苏氨酸/酪氨酸激酶 1 (STYK1) 是一种受体蛋白酪氨酸激酶 (RPTK) 样分子，可在多个人体器官中检测到。 STYK1在促进多种癌症的发生和转移中发挥重要作用。通过分析2013年免疫基因组计划数据库中免疫细胞中RTK的表达情况，我们发现STYK1主要在NK细胞中表达。为了研究STYK1的功能，我们利用CRISPR/Cas9技术制备了STYK1缺失小鼠，我们发现STYK1缺失小鼠在无瘤静息状态下，脾脏和骨髓中的NK细胞数量、发育和功能均正常。为了检查STYK1在体内的肿瘤监测，我们利用了多种肿瘤模型，包括体内NK细胞特异性靶细胞（ß2M和RMA-S）清除实验、皮下和静脉注射B16F10黑色素瘤模型以及自发性乳腺癌症模型 MMTV-PyMT。令人惊讶的是，我们发现致癌STYK1的缺失促进了四种模型肿瘤的进展，并且与WT小鼠相比，我们观察到STYK1缺失小鼠的肿瘤组织中NK细胞积累减少。为了研究STYK1在NK中的作用机制，STYK1-/-和WT NK的RNA序列揭示了STYK1-/- NK细胞中与迁移和粘附相关的信号通路的差异。对与 NK 细胞迁移相关的趋化因子受体的进一步分析表明，STYK1 缺陷的 NK 细胞表现出 CCR2 表达显着降低。 STYK1 表达与神经胶质瘤患者的肿瘤进展呈负相关。总体而言，我们的研究发现 NK 细胞中 STYK1 的表达通过调节 CCR2 并渗透到肿瘤组织来介导 NK 细胞抗肿瘤反应。© 2024。作者。

The serine/threonine/tyrosine kinase 1 (STYK1) is a receptor protein-tyrosine kinase (RPTK)-like molecule that is detected in several human organs. STYK1 plays an important role in promoting tumorigenesis and metastasis in various cancers. By analyzing the expression of RTKs in immune cells in the database of 2013 Immunological Genome Project, we found that STYK1 was principally expressed in NK cells. In order to investigate the function of STYK1, we used CRISPR/Cas9 technology to generate STYK1-deleted mice, we found STYK1 deletion mice have normal number, development, and function of NK cells in spleen and bone marrow in tumor-free resting state. To examine the tumor surveillance of STYK1 in vivo, we utilized a variety of tumor models, including NK cell-specific target cell (ß2M and RMA-S) clearance experiments in vivo, subcutaneous and intravenous injection of B16F10 melanoma model, and the spontaneous breast cancer model MMTV-PyMT. Surprisingly, we discovered that deletion of the oncogenic STYK1 promoted the four-model tumor progression, and we observed a reduction of NK cell accumulation in the tumor tissues of STYK1 deletion mice compared to WT mice. In order to study the mechanism of STYK1 in NK, RNA sequence of STYK1-/- and WT NK have unveiled a disparity in the signaling pathways linked to migration and adhesion in STYK1-/- NK cells. Further analysis of chemokine receptors associated with NK cell migration revealed that STYK1-deficient NK cells exhibited a significant reduction in CCR2 expression. The STYK1 expression was negatively associated with tumor progression in glioma patients. Overall, our study found the expression of STYK1 in NK cell mediates NK cell anti-tumor response through regulating CCR2 and infiltrating into tumor tissue.© 2024. The Author(s).