Migration inhibition of water stress proteins from Nostoc commune Vauch. via activation of autophagy in DLD-1 cells

Int J Biol Macromol. 2018 Nov:119:669-676. doi: 10.1016/j.ijbiomac.2018.07.188. Epub 2018 Jul 30.

Abstract

Water stress proteins (WSP1) from Nostoc commune Vauch. had been proven to selectively induce colon cancer cells apoptosis. In this study, the effect of WSP1 on migration of human colon cancer cells was investigated. It showed that WSP1 inhibited DLD-1 cell migration, but with an insignificant effect on normal human colon epithelial cells. The data further indicated that WSP1 activated autophagy through down regulation of PI3K/AKT/mTOR pathway. Meanwhile, β‑catenin was degraded by autophagy, which then restrained epithelial-mesenchymal transition (EMT) of DLD-1 cell and its migration was subsequently suppressed significantly. The same changes occurred in xenografted nude mice according to the obtained immunohistochemical results. Consistently, the application of autophagy inhibitor largely reversed the inhibited migration by WSP1 treatment. Taken together, WSP1 could suppress migration of DLD-1 cells by autophagy inhibited EMT. The results suggested that WSP1 possessed the potential as a selective therapeutic agent against metastatic colon cancer.

Keywords: Autophagy; Colon cancer; EMT; Migration; Water stress protein 1.

MeSH terms

  • Autophagy / drug effects*
  • Bacterial Proteins / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Extracellular Matrix Proteins / pharmacology*
  • Humans
  • Nostoc commune / chemistry*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • beta Catenin / metabolism

Substances

  • Bacterial Proteins
  • Extracellular Matrix Proteins
  • beta Catenin
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases