Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Obstetrics and Gynecology, Taizhou Women and Children's Hospital of Wenzhou Medical University, Taizhou, Zhejiang, China.
Mol Carcinog. 2023 Aug;62(8):1147-1162. doi: 10.1002/mc.23552. Epub 2023 May 3.
SH3 domain-binding kinase 1 (SBK1), is a member of the serine/threonine protein kinases family, and was confirmed to be upregulated in cervical cancer in our previous study. Nonetheless, the role of SBK1 in regulating cancer occurrence and development is unclear. In this study, the stable SBK1-knockdown and -overexpressed cell models were constructed by plasmid transfection technology. Cell viability and growth were assessed through CCK-8, colony formation, and BrdU methods. Cell cycle and apoptosis were analyzed by flow cytometry. The JC-1 staining assay was used to explore mitochondrial membrane potential. The scratch and Transwell assays were used to evaluate the cell metastatic ability. The nude mice models were utilized to explore the SBK1 expression affecting tumor growth in vivo. Our research indicated a high expression of SBK1 both in tissues and cells of cervical cancer. The proliferative, migratory, as well as invasive capacities of cervical cancer cells, were suppressed, and apoptosis was enhanced after SBK1 silence, whereas SBK1 upregulation led to opposite results. In addition, Wnt/β-catenin and Raf/ERK1/2 pathways were activated by SBK1 upregulation. Furthermore, downregulation of c-Raf or β-catenin, reversed the proliferation promotion and apoptosis inhibition effects in SBK1-overexpressed cells. The same results were observed with the use of the specific Raf inhibitor. SBK1 overexpression also contributed to tumor growth in vivo. Overall, SBK1 played a vital role in cervical tumorigenesis via activating the Wnt/β-catenin and Raf/ERK1/2 pathways.
SH3 结构域结合激酶 1（SBK1）是丝氨酸/苏氨酸蛋白激酶家族的成员，在我们之前的研究中证实其在宫颈癌中上调。然而，SBK1 在调节癌症发生和发展中的作用尚不清楚。在这项研究中，通过质粒转染技术构建了稳定的 SBK1 敲低和过表达细胞模型。通过 CCK-8、集落形成和 BrdU 方法评估细胞活力和生长。通过流式细胞术分析细胞周期和凋亡。使用 JC-1 染色法探讨线粒体膜电位。通过划痕和 Transwell 测定评估细胞迁移能力。利用裸鼠模型探讨 SBK1 表达对体内肿瘤生长的影响。我们的研究表明，宫颈癌组织和细胞中 SBK1 表达水平较高。沉默 SBK1 后，宫颈癌细胞的增殖、迁移和侵袭能力受到抑制，凋亡增强，而 SBK1 过表达则导致相反的结果。此外，SBK1 上调激活了 Wnt/β-catenin 和 Raf/ERK1/2 通路。此外，下调 c-Raf 或 β-catenin 可逆转 SBK1 过表达细胞中增殖促进和凋亡抑制的作用。使用特定的 Raf 抑制剂也观察到了相同的结果。SBK1 过表达也有助于体内肿瘤生长。总之，SBK1 通过激活 Wnt/β-catenin 和 Raf/ERK1/2 通路在宫颈癌发生中发挥重要作用。
