Sialyltransferases and Neuraminidases: Potential Targets for Cancer Treatment

Abstract

Cancers are the leading cause of death, causing around 10 million deaths annually by 2020. The most common cancers are those affecting the breast, lungs, colon, and rectum. However, it has been noted that cancer metastasis is more lethal than just cancer incidence and accounts for more than 90% of cancer deaths. Thus, early detection and prevention of cancer metastasis have the capability to save millions of lives. Finding novel biomarkers and targets for screening, determination of prognosis, targeted therapies, etc., are ways of doing so. In this review, we propose various sialyltransferases and neuraminidases as potential therapeutic targets for the treatment of the most common cancers, along with a few rare ones, on the basis of existing experimental and in silico data. This compilation of available cancer studies aiming at sialyltransferases and neuraminidases will serve as a guide for scientists and researchers working on possible targets for various cancers and will also provide data about the existing drugs which inhibit the action of these enzymes.

Potassium Channels, Glucose Metabolism and Glycosylation in Cancer Cells

“…In particular, the negatively charged sialic acid present in glycans affects the electrical excitability of cells [230]. Altered sialylation occurs in most cancer cells, and the presence of sialic acid-containing tumor antigens correlates with poor survival [231]. Inhibition of sialization reduces metastasis and increases cell sensitivity to chemotherapy and radiotherapy [232].…”

Cell Membrane Sialome: Sialic Acids as Therapeutic Targets and Regulators of Drug Resistance in Human Cancer Management

“…Given the chemical and physical properties of sialic acids and their modulatory influence on protein function and structure, membrane sialoglycans can the regulate cellular sensitivity to drugs through the direct influence on drug activity, the drug's reduced ability to bind to hypersialylated cancer cells, and the modification of the function of proteins related to cell division. However, evidence has been provided that aberrant sialylation, and especially sialyltransferases overexpression, and the abnormal (usually decreased) expression of sialidases contribute to therapy resistance in cancer [118]. Changes in the sialylation pattern have been detected in cells and tissues exposed to various stimulatory agents, including ethanol, heavy metal stress hormones, and narcotic substances as a result of an altered balance between activities and the expression sialyltransferases and sialidases [119][120][121][122][123].…”

Structural and functional characterization of cold-active sialidase isolated from Antarctic fungus Penicillium griseofulvum P29

“…Despite of intensive search for cold-active enzymes, there are no reports of Antarctic microbial (bacterial or fungal) producers of sialidase. Sialidases (neuraminidases, N-acetylneuraminic acid hydrolases, EC 3.2.1.18) are the enzyme family of glycohydrolytic enzymes that remove sialic acid residues from various sialoderivatives [ 20 ]. They hydrolyze terminal N- or O-acylneuraminic acids, which are α(2,3)-, α(2,6)-, α(2,8)- or α(2,9)-linked to glycoproteins, glycolipids, polysaccharides, mucopolysaccharides, and oligosaccharides.…”