Microcystin-LR induced microfilament rearrangement and cell invasion by activating ERK/VASP/ezrin pathway in DU145 cells

Toxicon. 2022 Apr 30:210:148-154. doi: 10.1016/j.toxicon.2022.02.023. Epub 2022 Mar 3.

Abstract

Microcystin-LR (MC-LR) is an environmental toxin that is synthesized by cyanobacteria and considered a potential human carcinogen. However, the role of MC-LR in prostate cancer progression has not been elucidated. The purpose of this study was to investigate the effect of MC-LR on prostate cancer cell invasion and its underlying mechanisms. Transwell assay was performed, and the result showed that MC-LR increased DU145 cell invasion in a concentration-dependent manner. The result of Western blot showed that MC-LR promoted ERK phosphorylation, while enhancing VASP and ezrin phosphorylation. Moreover, PD0325901 was used to verify the role of the ERK/VASP/ezrin axis in MC-LR-promoted cell invasion. The results revealed that MC-LR promoted microfilament rearrangement and cell invasion by activating the ERK/VASP/ezrin pathway in DU145 cells. Finally, in vivo assay was performed, and the result suggested that MC-LR promoted p-ERK, p-VASP and p-ezrin expression and local invasion in nude mice model. Taken together, our data proved that MC-LR induced microfilament rearrangement and cell invasion by activating the ERK/VASP/ezrin pathway in DU145 cells.

Keywords: ERK; Invasion; MC-LR; Microfilament; Prostate cancer.

MeSH terms

  • Actin Cytoskeleton*
  • Animals
  • Cytoskeletal Proteins
  • Male
  • Marine Toxins
  • Mice
  • Mice, Nude
  • Microcystins* / toxicity

Substances

  • Cytoskeletal Proteins
  • Marine Toxins
  • Microcystins
  • ezrin
  • cyanoginosin LR