Glycosylation is catalyzed by various
glycosyltransferase enzymes which are mostly located in the Golgi apparatus in cells. These
enzymes glycosylate various complex
carbohydrates such as
glycoproteins,
glycolipids, and
proteoglycans. The
enzyme activity of
glycosyltransferases and their gene expression are altered in various pathophysiological situations including
cancer. Furthermore, the activity of
glycosyltransferases is controlled by various factors such as the levels of
nucleotide sugars, acceptor substrates,
nucleotide sugar transporters, chaperons, and endogenous
lectin in
cancer cells. The glycosylation results in various functional changes of
glycoproteins including
cell surface receptors and adhesion molecules such as
E-cadherin and
integrins. These changes confer the unique characteristic phenotypes associated with
cancer cells. Therefore,
glycans play key roles in
cancer progression and treatment. This review focuses on
glycan structures, their biosynthetic
glycosyltransferases, and their genes in relation to their
biological significance and involvement in
cancer, especially
cancer biomarkers, epithelial-mesenchymal transition,
cancer progression and
metastasis, and
therapeutics. Major N-
glycan branching structures which are directly related to
cancer are β1,6-GlcNAc branching, bisecting GlcNAc, and core
fucose. These structures are enzymatic products of
glycosyltransferases, GnT-V, GnT-III, and Fut8, respectively. The genes encoding these
enzymes are designated as MGAT5 (Mgat5), MGAT3 (Mgat3), and FUT8 (Fut8) in humans (mice in parenthesis), respectively. GnT-V is highly associated with
cancer metastasis, whereas GnT-III is associated with
cancer suppression. Fut8 is involved in expression of
cancer biomarker as well as in the treatment of
cancer. In addition to these
enzymes,
GnT-IV and GnT-IX (GnT-Vb) will be also discussed in relation to
cancer.