c-Jun-dependent β3GnT8 promotes tumorigenesis and metastasis of hepatocellular carcinoma by inducing CD147 glycosylation and altering N-glycan patterns

Abstract

β3GnT8, a key polylactosamine synthase, plays a vital role in progression of various types of human cancer. The role of β3GnT8 in hepatocellular carcinoma (HCC) and the underlying mechanisms, however, remain largely unknown. In this study, we found that β3GnT8 and polylactosamine were highly expressed in HCC tissues compared with those in adjacent paracancer tissues. Overexpression of β3GnT8 promoted while knockdown of β3GnT8 inhibited HCC cell invasion and migration in vitro. Importantly, enhanced tumorigenesis was observed in nude mice inoculated with β3GnT8-overexpressing HCC cells, suggesting that β3GnT8 is important for HCC development in vitro and in vivo. Mechanistically, β3GnT8 modulated the N-glycosylation patterns of CD147 and altered the polylactosamine structures in HCC cells by physically interacting with CD147. In addition, our data showed the c-Jun could directly bind to the promoter of β3GnT8 gene and regulate β3GnT8 expression. β3GnT8 regulated HCC cell invasion and migration in a C-Jun-dependent manner. Collectively, our study identified β3GnT8 as a novel regulator for HCC invasion and tumorigenesis. Targeting β3GnT8 may be a potential therapeutic strategy against HCC.

Identification of LCA-binding Glycans as a Novel Biomarker for Esophageal Cancer Metastasis using a Lectin Array-based Strategy

“…CD147, also known as EMMPRIN, Basign, and HAb18G, is a widely expressed cell surface protein with multiple glycosylated forms. Previous studies have shown that lectins PHA-L, PHA-E, and LEL could directly bind to CD147 in many types of cancer cells [12,34,35]. In the present study, we identified CD147 as a lectin LCA-recognized membrane glycoprotein in EC cells.…”

Knockdown of Oligosaccharyltransferase Subunit Ribophorin 1 Induces Endoplasmic-Reticulum-Stress-Dependent Cell Apoptosis in Breast Cancer

“…Liu et al found that the N-glycan profiles of membrane proteins in BC tissues significantly changed compared to the adjacent normal ones (40). Furthermore, previous reports have demonstrated the N-glycan alterations were essential for tumorigenesis, proliferation, and metastasis via modifying critical proteins or triggering mechanisms involved in the maintenance of cell homeostasis, such as ERS (41)(42)(43)(44)(45). The 12 known subunits of OST complex play different roles in N-glycosylation.…”

Retracted: The long noncoding RNA cardiac hypertrophy‐related factor plays oncogenic roles in hepatocellular carcinoma by downregulating microRNA‐211

“…Many factors contribute to the occurrence of HCC, such as DNA mutation and methylation, hepatitis B virus infection, aflatoxin B1 exposure, and aberrant activation of multiple intracellular signaling pathways . Despite the development of standard treatment options, including tumor resection, percutaneous radiofrequency ablation, chemotherapy, and liver transplantation, there are still many patients who present insufficient response to therapy . It is worthy to note that a more clear understanding of pathogenesis of HCC will be helpful for defining the effective diagnostic and therapeutic targets for HCC.…”

“…[4][5][6][7] Despite the development of standard treatment options, including tumor resection, percutaneous radiofrequency ablation, chemotherapy, and liver transplantation, there are still many patients who present insufficient response to therapy. 8 It is worthy to note that a more clear understanding of pathogenesis of HCC will be helpful for defining the effective diagnostic and therapeutic targets for HCC.…”