Aberrant Expression of Sialidase in Cancer and Diabetes
Altered sialylation is associated with malignant properties such as invasiveness and metastasis. To understand the causes and the consequences of aberrant forms, our studies have focused on sialidases responsible for the removal of sialic acids from glycoproteins and glycolipids. Mammalian sialidases have been classified into four types (designated as Neu1, Neu2, Neu3, and Neu4) differing in subcellular localization and enzymatic properties. We found that the four types behave in different manners during carcinogenesis (Miyagi et al. 2004). Among the sialidases, Neu3 is a key enzyme for ganglioside degradation and is unique in being localized mainly in the plasma membrane and in hydrolyzing specifically gangliosides, thereby probably participating in cell surface events including neuronal differentiation and transmembrane signaling. The human Neu3 ortholog, NEU3, is indeed upregulated in various cancers where it suppresses apoptosis. Its overexpression in mice results in a diabetic phenotype. Herein molecular mechanisms and significance of aberrant expression of NEU3 are briefly introduced.
KeywordsSialic Acid Insulin Signaling Sodium Butyrate Diabetic Phenotype Malignant Property
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