PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth

Int J Mol Sci. 2019 Jan 11;20(2):275. doi: 10.3390/ijms20020275.

Abstract

PPP3CB belongs to the phosphoprotein phosphatases (PPPs) group. Although the majority of the PPP family play important roles in the epithelial-to-mesenchymal transition (EMT) of tumor cells, little is known about the function of PPP3CB in the EMT process. Here, we found PPP3CB had high expression in kidney mesenchymal-like cells compared with kidney epithelial-like cells. Knock-down of PPP3CB downregulated epithelial marker E-cadherin and upregulated mesenchymal marker Vimentin, promoting the transition of cell states from epithelial to mesenchymal and reorganizing the actin cytoskeleton which contributed to cell migration. Conversely, overexpression of PPP3CB reversed EMT and inhibited migration of tumor cells. Besides, in vitro and in vivo experiments indicated that the loss of PPP3CB suppressed the tumor growth. However, the deletion of the phosphatase domain of PPP3CB showed no effect on the expression of E-cadherin, migration, and G401 cell proliferation. Together, we demonstrate that PPP3CB inhibits G401 cell migration through regulating EMT and promotes cell proliferation, which are both associated with the phosphatase activity of PPP3CB.

Keywords: PPP3CB; epithelial–mesenchymal transition; metastasis; proliferation.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Calcineurin / genetics*
  • Calcineurin / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Mice
  • Neoplasm Transplantation
  • Up-Regulation
  • Vimentin / genetics

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • VIM protein, human
  • Vimentin
  • Calcineurin
  • PPP3CB protein, human