Glycosylation changes leading to the increase in size on the common core of N-glycans, required enzymes, and related cancer-associated proteins

Abstract

Glycan parts of glycoconjugates on the surfaces of cells regulate many kinds of interactions between the cells and their immediate environments. Alterations in glycosylation on the cancer-associated glycoproteins are responsible for changes in their molecular interactions and biological functions. Glycosylation changes occur in the core and/or at the nonreducing end of the oligosaccharide chains of N-glycans. In this review, we focus on the branching of the common core structure of N-glycans, the responsible enzyme, and the extensions of some of the branches causing size increases on the surface of tumor cells. Abnormal branching, elongation of the branches, and increasing size of the common core of N-glycans are the typical features of these changes and are related with malignant transformations. Seven N-acetylglucosaminyltransferases (GnTs) (GnT-I, GnT-II, GnT-III, GnT-IV, GnT-V, GnT-VI, and GnT-IX) and α1,6-fucosyltransferase (FUT8) initiate the new branches on the core. GnT-IV, GnT-V, and GnT-IX initiate the branches available for poly-LacNAc extensions, which are responsible for tumor progression and metastasis. GnT-III prevents the catalytic activity of GnT-II, GnT-IV, GnT-V, and FUT8 to form branching and elongation of the branches. The contributions of GnT-III and the other enzymes to the cancer progression are in conflict with each other. While GnT-III prevents cancer, the others increase metastasis. The function of FUT8 is related to signal transduction and its activity is higher in tumor tissue than in healthy tissue. The impact of glycosylation changes on some of the cancer-associated proteins (growth factor receptors, adhesion and signal molecules, CD147, TIMP-1, and matriptase) is also summarized.

Diverse expression of N-acetylglucosaminyltransferase V and complex-type β1,6-branched N-glycans in uveal and cutaneous melanoma cells

“…Changes in the amount and composition of complex-type structures have been frequently observed in the transformation and progression of different types of tumors (Laidler & Lityńska, 1997;Taniguchi & Korekane, 2011), including melanoma (Pocheć et al, 2003;Przybyło et al, 2007;Pocheć et al, 2013). The increase in the size of N-glycans is the result of increased branching of complex-type structures (Kim & Varki, 1997;Karaçali et al, 2014). One of the most commonly observed changes in the glycosylation profile of tumor cells is an enhanced synthesis of the antenna linked β1,6 to the core structure of N-glycans (Dennis et al, 1987;Lityńska et al, 2008).…”

Human embryonic stem cell N-glycan features relevant to pluripotency

“…An increase of 14% for the embryoid body and 22% for further differentiated cells was observed (Satomaa et al, 2009). The number of poly-N-acetyllactosaminyl chains on the core branches was associated with differentiated cells (Karaçalı et al, 2014). An increase in poly-N-acetyllactosaminyl repeats occurred in embryonic stem cells during differentiation (Wearne et al, 2006).…”

Determination of sialic acids in the nervous system of silkworm (Bombyx mori L.): Effects of aging and development

“…Mammals also form α2,8linked sialic acid homopolymer known as polysialic acid (PSA), which is found in neural cell adhesion molecules (NCAM), and plays many roles in NCAM adhesion, neurite outgrowth and cell migration [10]. Sialic acids have received much attention to date be-cause they participate in the pathogenesis of many diseases such as cancer [11][12][13][14][15], inflammatory diseases [16][17][18][19] and viral infections [20][21][22][23][24][25]. Our knowledge of this important carbohydrate family has improved with advances in the development of sialic acid analogs [11].…”