Mitochondrial fission regulator 2 (MTFR2) promotes growth, migration, invasion and tumour progression in breast cancer cells

Aging (Albany NY). 2019 Nov 18;11(22):10203-10219. doi: 10.18632/aging.102442. Epub 2019 Nov 18.

Abstract

Introduction: Mitochondrial fission regulator 2 (MTFR2) belongs to the MTFR family, and 2 isoforms of MTFR2 are produced by alternative splicing. The role of MTFR2 in breast cancer (BC) remains unknown.

Results: MTFR2 was upregulated in BC tissues and was strongly associated with tumor characteristics. Moreover, Kaplan-Meier and Cox proportional hazards analyses indicated that high MTFR2 expression was related to poor overall survival. In addition, the capacity for migration and invasion decreased in two BC cell lines after knockdown of MTFR2. The epithelial-mesenchymal transition pathway was inhibited in MTFR2-silenced cells. MTFR2 can switch glucose metabolism from OXPHS to glycolysis in a HIF1α- and HIF2α-dependent manner.

Conclusion: Taken together, our results indicate that increased expression of MTFR2 is associated with tumour progression in breast cancer cells through switching glucose metabolism from OXPHS to glycolysis in a HIF1α- and HIF2α-dependent manner.

Materials and methods: We obtained data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to analyse MTFR2 expression in BC. The prognostic value of MTFR2 expression was assessed using the Kaplan-Meier method. The biological influence of MTFR2 on BC cell lines was studied using proliferation, Transwell migration, invasion and mitochondrial function assays.

Keywords: MTFR2; breast cancer; glycolysis; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Up-Regulation*

Substances

  • Biomarkers, Tumor
  • GTP Phosphohydrolases
  • MTG1 protein, human