CK2 causes stemness and chemotherapy resistance in liver cancer through the Hedgehog signaling pathway

Background: Liver cancer is one of the major causes of cancer-related deaths globally. Cancer cell stemness and chemotherapy resistance contribute to the high mortality. Although evidence indicates that the alpha subunit of protein kinase 2 (CK2 alpha) is involved in several human cancers, its function in liver cancer remains unknown. In the present study, we aimed to elucidate the role of CK2 alpha in liver cancer. Methods: We examined the role of CK2 alpha regulation in stemness and chemotherapy resistance capacity of liver cancer cells. MTT assays, tumor sphere formation assays, RT-PCR, flow cytometry, Western blotting assay, clonogenicity assay, matrigel invasion assay and bioinformatics were conducted in this study. Results: CK2 alpha expression in the liver cancer tissues was notably upregulated compared with that in the corresponding non-tumorous tissues. The overexpression of CK2 alpha promoted tumor sphere formation, increased the percentage of CD133(+) and side population cells, caused the resistance of liver cancer cells to 5-FU treatment, increased the expression levels of NANOG, OCT4, SOX2, Gli1 and Ptch1, and enhanced the ability of CD133(+) cell clone formation and invasion. Consistently, the downregulation of CK2 alpha had the opposite effects. CK2asilencing inhibited the Hedgehog pathway by reducing the expression of Gli1 and Ptch1. Mechanistically, CK2 alpha regulation on liver cancer cell stemness and chemotherapy resistance was found to be involved in the Hedgehog signaling pathway. Conclusions: Our study may bring some new insights into the occurrence of liver cancer. Furthermore, these findings suggest that targeting CK2 alpha may be a novel therapeutic strategy for patients with liver cancer. (c) 2021 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.