Abstract
Among the various posttranslational modification reactions, glycosylation is the most common, and nearly 50% of all known proteins are thought to be glycosylated. In fact, changes in glycosylation readily occur in carcinogenesis, invasion and metastasis. This report investigated the modification of glycosylation mediated the invasive properties of Hca-F and Hca-P murine hepatocarcinoma cell lines, which have high, low metastatic potential in the lymph nodes, respectively. Analysis revealed that the N-glycan composition profiling, expression of glycogenes and lectin binding profiling were different in Hca-F cells, as compared to those in Hca-P cells. Further analysis of the N-glycan regulation by tunicamycin (TM) application or PNGase F treatment in Hca-F cells showed partial inhibition of N-glycan glycosylation and decreased invasion both in vitro and in vivo. We targeted glycogene ST6GAL1, which was expressed differently in Hca-F and Hca-P cells, and regulated the expression of ST6GAL1. The altered levels of ST6GAL1 were also responsible for changed invasive properties of Hca-F and Hca-P cells both in vitro and in vivo. These findings indicate a role for glycosylation modification as a mediator of tumor lymphatic metastasis, with its altered expression causing an invasive ability differentially.
Highlights
It is well known that glycosylation affects many physicochemical properties of glycoproteins
We mainly focused on the modification of N-glycan of cell surface to further address the important roles of glycosylation in lymphatic metastasis of murine hepatocarcinoma cells
CD147 is a highly N-glycosylated immunoglobulin superfamily transmembrane protein that is composed of two extracellular Ig domains, which contributes to a highly N-glycosylated form, HG-CD147 (,40–60 kDa) and lowly glycosylated form, LG-CD147 (,32 kDa) [19]
Summary
It is well known that glycosylation affects many physicochemical properties of glycoproteins. Modified oligosaccharides affect protein folding and stability, and as a result, regulate many physiological and pathological events, including cell growth, migration, differentiation, and tumor metastasis [1,2,3,4]. It is not surprising that aberrant glycosylation patterns can be considered to have great potential as therapeutic targets or clinical biomarkers for early detection, diagnosis and monitoring of cancer treatment. Specific changes in the glycosylation pattern of cell surface glycoproteins have been shown to correlate with the enhancement of the metastatic efficiency of tumor cells [5]. There is ample evidence that altered N-glycosylation patterns are present on tumor cells and these findings have sparked the search for glycan based biomarkers for the detection of different types of cancer [6–
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