alpha 2,6-Sialylation mediates hepatocellular carcinoma growth in vitro and in vivo by targeting the Wnt/beta-catenin pathway

作者：Zhao, Y.; Wei, A.; Zhang, H.; Chen, X.; Wang, L.; Zhang, H.; Yu, X.; Yuan, Q.; Zhang, J.^*; Wang, S.^*

来源：Oncogenesis, 2017, 6(5): e343.

DOI：10.1038/oncsis.2017.40

• SIGNALING PATHWAY
• SIALIC ACIDS
• CELL-DEATH
• CANCER
• EXPRESSION
• GLYCOSYLATION
• PROGRESSION
• MECHANISMS
• GLYCANS
• PROMOTES

Abnormal sialylation due to overexpression of sialyltransferases has been associated with tumorigenesis and tumor progression. Although ST6Gal-I influences cancer persistence and progression by affecting various receptors, the underlying mechanisms and mediators remain largely obscure, especially in hepatocellular carcinoma (HCC). We found that ST6Gal-I expression was markedly upregulated in HCC tissues and cells, high levels being associated with aggressive phenotype and poor prognosis. Furthermore, we examined the roles and mechanisms of ST6Gal-I in HCC tumorigenesis and metastasis in vitro and in vivo. ST6Gal-I overexpression promoted proliferation, migration and invasion of Huh-7 cells, whereas its knockdown restricted these abilities in MHCC97-H cells. Additionally, in a mouse xenograft model, ST6Gal-I-knockdown MHCC97-H cells formed significantly smaller tumors, implying that ST6Gal-I overexpression can induce HCC cell malignant transformation. Importantly, enhanced HCC tumorigenesis and metastasis by ST6Gal-I may be associated with Wnt/beta-catenin signaling promotion, including beta-catenin nuclear transition and upregulation of downstream molecules. Together, our results suggest a role for ST6Gal-I in promoting the growth and invasion of HCC cells through the modulation of Wnt/beta-catenin signaling molecules, and that ST6Gal-I might be a promising marker for prognosis and therapy of HCC.

• 出版日期2017-5
• 单位大连医科大学; 大连理工大学