Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously demonstrated that transfection of a sialidase cDNA into B16-BL6 cells, a highly metastatic and invasive cell line derived from the mouse B16 melanoma, resulted in a marked suppression of metastasis accompanied by decreased cellular content of the GM3 that is one of the target molecules of the sialidase expressed (Tokuyama et al., 1997 Int. J. Cancer, 73, 410-415). To obtain further insight into the involvement of sialidase in metastasis, we made a comparison of the levels of sialidase activity and GM3 content between B16 melanoma cell lines with low (B16-F1) and high (B16-F10 and -BL6) metastatic potential. The cells exhibited sialidase activity towards 4-methylumbelliferyl N-acetylneuraminic acid (4MU-Neu5Ac) and gangliosides at acidic pH in the particulate fractions, but not in the cytosol. The activity toward 4MU-NeuAc was significantly lower in highly metastatic cells. The activity toward gangliosides, on the other hand, varied independently of metastatic potential: B16-F10 cells with a high potential for experimental metastasis showed the lowest level and B16-BL6 cells having high invasiveness had rather a higher level of ganglioside sialidase along with a much greater GM3 synthase activity than the other two cell lines. Flow cytometric analysis with anti-GM3 antibody revealed that highly metastatic cell lines were higher in the binding affinity as compared to B16-F1 cells, B16-BL6 cells containing twice as much cellular GM3 as B16-F1 cells on thin-layer chromatography.
 ...
PMID:Comparative study of sialidase activity and G(M3) content in B16 melanoma variants with different metastatic potential. 982 65

Human plasma membrane-associated sialidase (NEU3), a key enzyme for ganglioside degradation, is markedly upregulated in human cancers, leading to apoptosis suppression. To define molecular mechanisms and the possible target for NEU3, its encoding gene was silenced by small interference RNA (siRNA) or overexpressed in human cells. NEU3 siRNA-induced apoptosis with no special stimuli in HeLa cells, accompanied with decreased Bcl-xL and increased mda7 and GM3 synthase mRNA levels, whereas overexpression resulted in the opposite. Carcinoma HT-29 and MCF-7 cells appeared to be similarly affected, but normal cell lines demonstrated no significant changes. NEU3 siRNA was found to inhibit and NEU3 overexpression to stimulate Ras activation with consequent influence on extracellular signal-regulated kinases and Akt. Ras activation by NEU3 was abrogated by PP2 (src inhibitor) or AG1478 (epidermal growth factor receptor (EGFR) inhibitor), and NEU3 actually enhanced EGF-stimulated tyrosine-phosphorylation of EGFR, suggesting that the upstream targets might be tyrosine kinases including src and EGFR, and the subsequent stimulation of Ras cascade leads to the inhibition of cell apoptosis. Glycolipid changes observed seemed to be one of the causes of the cell effects. NEU3 may thus be an essential gene for cancer cell survival and siRNAs targeting this protein could have utility for gene-based therapy of human cancers.
 ...
PMID:A crucial role of plasma membrane-associated sialidase in the survival of human cancer cells. 1733 92

Our studies during the early 1970s showed that expression of GM3, the simplest ganglioside and an abundant animal cell membrane component, is reduced during malignant transformation of cells by oncogenic viruses. Levels of mRNA for GM3 synthase were reduced in avian and mammalian cells transformed by oncoprotein "v-Jun", and overexpression of GM3 synthase in the transformed cells caused reversion from transformed to normal cell-like phenotype. GM3 has a well-documented inhibitory effect on activation of growth factor receptors (GFRs), particularly epidermal GFR (EGFR). De-N-acetyl GM3, which is expressed in some invasive human cancer cells, has an enhancing effect on EGFR activation. The important role of the sialosyl group of GM3 was demonstrated using NEU3, a plasma membrane-associated sialidase that selectively remove sialic acids from gangliosides GM3 and GD1a and is up-regulated in many human cancer cells. GM3 is highly enriched in a type of membrane microdomain termed "glycosynapse", and forms complexes with co-localized cell signaling molecules, including Src family kinases, certain tetraspanins (e.g., CD9, CD81, CD82), integrins, and GFRs (e.g., fibroblast growth factor receptor and hepatocyte growth factor receptor c-Met). Studies by our group and others indicate that GM3 modulates cell adhesion, growth, and motility by altering molecular organization in glycosynaptic microdomains and the activation levels of co-localized signaling molecules that are involved in cancer pathogenesis.
...
PMID:GM3 and cancer. 2561 25