Neuraminidase-1: A Sialidase Involved in the Development of Cancers and Metabolic Diseases.

Abstract

Simple SummaryCancers and metabolic diseases represent a leading cause of death in both developing and developed countries. Thus, new diagnostic and prognostic targets are urgently required. NEU-1 is a sialidase which regulates many membrane receptors through desialylation which results in either the activation or inhibition of the receptors. At the plasma membrane, NEU-1 is the catalytic subunit of the elastin receptor complex. This sialidase is not only required for the biological effects that are mediated by the elastin-derived peptides on several metabolic disorders, but NEU-1 is also involved in the development of various cancers. The aim of this review is to describe the role of NEU-1 in several metabolic diseases and cancers and to show that this protein could be considered in some cases as a link between these two physiopathological contexts. Consequently, NEU-1 could represent a common pharmacological target to treat putative metabolic syndrome-associated cancers like colorectal, hepatocellular and postmenopausal breast cancer.Sialidases or neuraminidases (NEU) are glycosidases which cleave terminal sialic acid residues from glycoproteins, glycolipids and oligosaccharides. Four types of mammalian sialidases, which are encoded by different genes, have been described with distinct substrate specificity and subcellular localization: NEU-1, NEU-2, NEU-3 and NEU-4. Among them, NEU-1 regulates many membrane receptors through desialylation which results in either the activation or inhibition of these receptors. At the plasma membrane, NEU-1 also associates with the elastin-binding protein and the carboxypeptidase protective protein/cathepsin A to form the elastin receptor complex. The activation of NEU-1 is required for elastogenesis and signal transduction through this receptor, and this is responsible for the biological effects that are mediated by the elastin-derived peptides (EDP) on obesity, insulin resistance and non-alcoholic fatty liver diseases. Furthermore, NEU-1 expression is upregulated in hepatocellular cancer at the mRNA and protein levels in patients, and this sialidase regulates the hepatocellular cancer cells’ proliferation and migration. The implication of NEU-1 in other cancer types has also been shown notably in the development of pancreatic carcinoma and breast cancer. Altogether, these data indicate that NEU-1 plays a key role not only in metabolic disorders, but also in the development of several cancers which make NEU-1 a pharmacological target of high potential in these physiopathological contexts.