SH3 domain‐binding kinase 1 promotes proliferation and inhibits apoptosis of cervical cancer via activating the Wnt/β‐catenin and Raf/ERK1/2 signaling pathways

Abstract

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.