Isoenzyme-Selective Inhibitors of Human Neuraminidases Reveal Distinct Effects on Cell Migration.
Md Amran HowladerTianlin GuoRadhika ChakrabertyChristopher W CairoPublished in: ACS chemical biology (2020)
The human neuraminidase enzymes (NEU1, NEU2, NEU3, and NEU4) are a class of enzymes implicated in pathologies including cancer and diabetes. Several reports have linked neuraminidase activity to the regulation of cell migration in cancer cells. Using an in vitro cell migration assay on fibronectin (FN) coated surfaces, we have investigated the role of these enzymes in integrin-mediated cell migration. We observed that neuraminidase inhibition caused significant retardation of cell migration in breast cancer (MDA-MB-231) and prostate cancer (PC-3) cell lines when using inhibitors of NEU3 and NEU4. In contrast, inhibition of NEU1 caused a significant increase in cell migration for the same cell lines. We concluded that the blockade of human neuraminidase enzymes with isoenzyme-selective inhibitors can lead to disparate results and has significant potential in the development of anticancer or wound healing therapeutics.
Keyphrases
- cell migration
- endothelial cells
- prostate cancer
- induced pluripotent stem cells
- pluripotent stem cells
- emergency department
- wound healing
- small molecule
- magnetic resonance imaging
- computed tomography
- genome wide
- adipose tissue
- cell proliferation
- pseudomonas aeruginosa
- high throughput
- adverse drug
- climate change
- glycemic control
- insulin resistance
- lymph node metastasis
- childhood cancer
- cell cycle arrest