Dephosphorylation of Girdin by PP2A inhibits breast cancer metastasis

Biochem Biophys Res Commun. 2019 May 21;513(1):28-34. doi: 10.1016/j.bbrc.2019.03.167. Epub 2019 Mar 29.

Abstract

Dysfunction of Girdin plays a crucial role in the development of a variety of tumors. Phosphorylated regulation of Girdin has been studied extensively. However, how Girdin is dephosphorylated remains unclear. In this study, we report a mechanism of Girdin dephosphorylation and the importance of this mechanism in the migration of breast cancer cells. We show that the protein phosphatase 2A (PP2A) complex can bind to Girdin via the modulating B subunit. Overexpression or knockdown of PP2A inhibits or increases the phosphorylation of Girdin at serine 1416, respectively. PP2Ac-induced Girdin dephosphorylation is involved in the inhibition of breast cancer cell migration. Furthermore, in human breast cancer samples, PP2Ac expression is negatively correlated with the phosphorylation of Girdin, and low expression of PP2Ac is correlated with tumor stage, grade and lymph node metastasis of breast cancer. These data indicate that PP2A regulates Girdin dephosphorylation and highlight the critical role of this pathway in breast cancer metastasis.

Keywords: Breast cancer; Girdin; Migration; PP2A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Lymphatic Metastasis / pathology
  • Microfilament Proteins / metabolism*
  • Neoplasm Metastasis / pathology
  • Phosphorylation
  • Protein Interaction Maps
  • Protein Phosphatase 2 / metabolism*
  • Vesicular Transport Proteins / metabolism*

Substances

  • CCDC88A protein, human
  • Microfilament Proteins
  • Vesicular Transport Proteins
  • Protein Phosphatase 2