Aberrant expression of sialidase in cancer

When cells undergo oncogenic transformation, the sialylation of cell surface glycoconjugates is altered, which is thought to be associated with malignant phenotype. To elucidate the significance and the molecular mechanism of the alteration, we have been focusing on sialidase that catalyzes the removal of sialic acid residues from glycoproteins and glycolipids. In mammalian cells, four types of sialidases have been identified to date and were found to behave in different manners during carcinogenesis. A sialidase found in lysosomes is decreased in the activity and mRNA level in cancer cells, while a sialidase in plasma membrane is increased as compared with those in the control cells. The former sialidase affects anchor-age-independent growth and metastatic ability and introduction of the sialidase gene leads to reversion of these phenotypes. On the other hand, the latter brings about suppression of apoptosis in cancer cells and knocking down of this gene with short interfering RNA results in acceleration of apoptosis. In this review, we describe and summarize the alteration of sialidases and its possible significance in carcinogenesis.