2. Academic Validation
  3. N-glycosylation by N-acetylglucosaminyltransferase IVa enhances the interaction of integrin β1 with vimentin and promotes hepatocellular carcinoma cell motility

N-glycosylation by N-acetylglucosaminyltransferase IVa enhances the interaction of integrin β1 with vimentin and promotes hepatocellular carcinoma cell motility

  • Biochim Biophys Acta Mol Cell Res. 2023 Oct;1870(7):119513. doi: 10.1016/j.bbamcr.2023.119513.
Depeng Yang 1,  Fang Han 1,  Jialing Cai 1,  Handi Sun 1,  Fengyou Wang 1,  Meiyi Jiang 1,  Mengmeng Zhang 1,  Mengfan Yuan 1,  Wenyang Zhou 1,  Huaxin Li 1,  Lijun Yang 1,  Yan Bai 1,  Lixing Xiao 1,  Haiyang Dong 1,  Qixiang Cheng 1,  Haoyu Mao 1,  Lu Zhou 1,  Ruonan Wang 1,  Yu Li 2,  Huan Nie 3
Affiliations

Affiliations

  • 1 School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China.
  • 2 School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China. Electronic address: liyugene@hit.edu.cn.
  • 3 School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China. Electronic address: nh1212@hit.edu.cn.
PMID: 37295747 DOI: 10.1016/j.bbamcr.2023.119513
Abstract

N-glycosylation has been revealed to be tightly associated with Cancer metastasis. As a key transferase that catalyzes the formation of β1,4 N-acetylglucosamine (β1,4GlcNAc) branches on the mannose core of N-glycans, N-acetylglucosaminyltransferase IVa (GnT-IVa) has been reported to be involved in hepatocellular carcinoma (HCC) metastasis by forming N-glycans; however, the underlying mechanisms are largely unknown. In the current study, we found that GnT-IVa was upregulated in HCC tissues and positively correlated with worse outcomes in HCC patients. We found that GnT-IVa could promote tumor growth in mice; notably, this effect was attenuated after mutating the enzymatic site (D445A) of GnT-IVa, suggesting that GnT-IVa regulated HCC progression by forming β1,4GlcNAc branches. To mechanistically investigate the role of GnT-IVa in HCC, we conducted GSEA and GO functional analysis as well as in vitro experiments. The results showed that GnT-IVa could enhance HCC cell migration, invasion and adhesion ability and increase β1,4GlcNAc branch glycans on Integrin β1 (ITGB1), a tumor-associated glycoprotein that is closely involved in cell motility by interacting with vimentin. Interruption of β1,4GlcNAc branch glycan modification on ITGB1 could suppress the interaction of ITGB1 with vimentin and inhibit cell motility. These results revealed that GnT-IVa could promote HCC cell motility by affecting the biological functions of ITGB1 through N-glycosylation. In summary, our results revealed that GnT-IVa is highly expressed in HCC and can form β1,4GlcNAc branches on ITGB1, which are essential for interactions with vimentin to promote HCC cell motility. These findings not only proposed a novel mechanism for GnT-IVa in HCC progression but also revealed the significance of N-glycosylation on ITGB1 during the process, which may provide a novel target for future HCC therapy.

Keywords

Cell motility; Hepatocellular carcinoma; Integrin β1; N-acetylglucosaminyltransferase IVa; N-glycosylation; Protein–protein interaction.

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