Phosphorylation of myofibrillogenesis regulator-1 activates the MAPK signaling pathway and induces proliferation and migration in human breast cancer MCF7 cells

FEBS Lett. 2014 Aug 25;588(17):2903-10. doi: 10.1016/j.febslet.2014.07.018. Epub 2014 Jul 24.

Abstract

Myofibrillogenesis regulator-1 (MR-1) has been characterized as a tumor promoter in many cancers. However, its mechanism of action has not been fully elucidated. Here, we report that MR-1 is overexpressed in human breast cancer cells and participates in tumor promotion in human breast cancer MCF7 cells by activating the ERK1/2 signaling pathway. MR-1 interacts with MEK1/2 and ERK1, and its N-terminal sequence plays a major role in promoting the MEK/ERK cascade. Furthermore, six phosphorylation sites of MR-1 were identified, and phosphorylation at S46 was shown to be critical for the activation of MEK/ERK. Therefore, our findings suggest that MR-1 functions as a tumor promoter in MCF7 cells by activating the MEK/ERK signaling.

Keywords: Breast cancer; ERK1; MEK1/2; Myofibrillogenesis regulator 1; Phosphorylation sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Breast Neoplasms / pathology*
  • Carcinogenesis
  • Cell Movement*
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • MAP Kinase Signaling System*
  • MCF-7 Cells
  • Muscle Proteins / deficiency
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Phosphorylation
  • RNA, Small Interfering / genetics

Substances

  • Muscle Proteins
  • PNKD protein, human
  • RNA, Small Interfering