Role of glycans in cancer cell death: A deadly relationship

Abstract

Cancer cells often rapidly proliferate and are resistant to the induction of cell death (apoptosis). The field of apoptosis control by glycans is still in the infant stages and requires much more research and knowledge of the biological functions of cell surface receptors. Extrinsic apoptosis is the cell death cascade initiated at the cell surface involving specific receptors, followed by recruitment of protein complexes and activation of proteins intracellularly that eventually lead to DNA breakage and cell death. The cell surface receptors that bind apoptosis-inducing ligands are glycoproteins, and a number of studies show that the glycans play a role in the expression, transport, oligomerization, or function of the receptors. Glycans can also be directly recognized by apoptosis-inducing lectins. Cancer cells often have specific alterations in these glycan structures. These abnormal glycans, and the enzymes that synthesize these glycans, may be partly responsible for the malfunctioning of apoptosis pathways. In particular, sialic acids and specific sialyltransferases are potential therapeutic targets to increase cell death. However, it is necessary to consider the glycosylation potentials of the specific cancer cells expressing the glycoproteins involved in apoptosis, such as Fas and receptors for tumor necrosis factor (TNF)α and TNF-related apoptosis-inducing ligand (TRAIL). Cells that undergo apoptosis also show altered expression and activities of glycosyltransferases. Technologies to alter cellular glycosylation may be successful in restoring apoptosis in cancer cells or in maintaining the populations of immune cells that eliminate cancer cells.