Abstract
Glycosylation alterations of cell surface proteins are often observed during the progression of malignancies. The specific cell surface N-glycans were profiled in hepatocellular carcinoma (HCC) with clinical tissues (88 tumor and adjacent normal tissues) and the corresponding serum samples of HCC patients. The level of core-α-1,6-fucosylated triantennary glycan (NA3Fb) increased both on the cell surface and in the serum samples of HCC patients (p < 0.01). Additionally, the change of NA3Fb was not influenced by Hepatitis B virus (HBV)and cirrhosis. Furthermore, the mRNA and protein expression of N-acetylglucosaminyltransferase IVa (GnT-IVa), which was related to the synthesis of the NA3Fb, was substantially increased in HCC tissues. Knockdown of GnT-IVa leads to a decreased level of NA3Fb and decreased ability of invasion and migration in HCC cells. NA3Fb can be regarded as a specific cell surface N-glycan of HCC. The high expression of GnT-IVa is the cause of the abnormal increase of NA3Fb on the HCC cell surface, which regulates cell migration. This study demonstrated the specific N-glycans of the cell surface and the mechanisms of altered glycoform related with HCC. These findings lead to better understanding of the function of glycan and glycosyltransferase in the tumorigenesis, progression and metastasis of HCC.
Highlights
It is urgent to study the molecular mechanism of hepatocellular carcinoma (HCC) and to find therapeutic targets and diagnosis mechanisms for effective medical treatment
The results revealed that NA3Fb was highly expressed on the cell surface of HCC cells (p < 0.01) and was increased in corresponding HCC patients’ serum samples (p < 0.01)
The results revealed that the level of NA2, NA3 and NA3Fb decreased along with cirrhosis and were increased in HCC (Fig. 2D), which indicated that NA2, NA3 and NA3Fb were not influenced by cirrhosis
Summary
It is urgent to study the molecular mechanism of HCC and to find therapeutic targets and diagnosis mechanisms for effective medical treatment. The majority of studies of glycosylation changes in HCC are conducted using patient serum samples[6]. DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE), which was developed by Callewaert, has been used to study the profile of serum as a robust, high-throughput, exceedingly sensitive, and reliable quantitative method[9,10]. We utilized this high-throughput glycomics method to profile cell surface-specific N-glycans from human breast cancer cell lines and tissues[11]. This study revealed significant connections between altered N-glycans and the tumorigenesis, progression and metastasis of HCC, indicating GnT-IVa as a therapeutic target for HCC treatment
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