In mammalian cells, four types of
sialidase have been described and found to behave in different ways during
carcinogenesis. We previously demonstrated that a human
sialidase associated with plasma membranes (NEU3) is up-regulated in human
colon cancer and is involved in suppression of apoptosis. Here we document altered expression of another human
sialidase, the recently identified NEU4, and evidence of its influence on the malignant phenotype in
colon cancers. Human colon mucosa was relatively rich in NEU4, which has been observed to possess short and long
isoforms, but hardly contained the latter form. In clear contrast to the NEU3 case, the levels of
mRNA for this
sialidase were found by quantitative RT-PCR to be markedly decreased in
colon cancers. In cultured human
colon cancer cells, the
enzyme was up-regulated in the early stage of apoptosis induced by either the death
ligand TRAIL or serum-depletion, and transfection of NEU4 resulted in acceleration of apoptosis and in decreased invasion and motility. The
siRNA-mediated NEU4 targeting, on the other hand, caused a significant inhibition of apoptosis and promotion of invasion and motility.
Lectin blot analyses revealed that desialylated forms of nearly 100 kDa
glycoproteins were prominently increased with PNA in NEU4 transfectants, whereas only slight changes in
glycolipids were detected as assessed by thin layer chromatography. These results suggest that NEU4 plays important roles for maintenance of normal mucosa mostly through desialylation of
glycoproteins and that down-regulation may contribute to invasive properties of
colon cancers.