Enolase-phosphatase 1 acts as an oncogenic driver in glioma

J Cell Physiol. 2021 Feb;236(2):1184-1194. doi: 10.1002/jcp.29926. Epub 2020 Jul 11.

Abstract

Enolase-phosphatase 1 (ENOPH1), a newly identified enzyme involved in l-methionine biosynthesis, is associated with anxiety and depression. In this study, ENOPH1 was found to play a crucial role in promoting the proliferation and migration of glioma cells. Among high-grade glioma patients, the overall survival of the group showing high ENOPH1 expression was shorter than that of the group showing low ENOPH1 expression. ENOPH1 knockdown inhibited glioma cell proliferation and migration. In parallel, ENOPH1 knockdown suppressed tumor growth capacity and prolonged survival in an orthotopic glioma model. Mechanistically, we found that ENOPH1 activates the PI3K/AKT/mTOR signaling pathway by regulating THEM4. In conclusion, ENOPH1 is an important mediator that promotes glioma cell proliferation and migration.

Keywords: AKT; ENOPH1; GSEA; RNA-seq; glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Middle Aged
  • Multienzyme Complexes / genetics*
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • RNA-Seq
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics
  • Thiolester Hydrolases / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • MASA enzyme, human
  • Membrane Proteins
  • Multienzyme Complexes
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • THEM4 protein, human
  • Thiolester Hydrolases