Metastatic TNBC is closely associated with a fused mitochondrial morphology and a glycolytic and lipogenic metabolism

Biochem Cell Biol. 2021 Aug;99(4):447-456. doi: 10.1139/bcb-2020-0439. Epub 2020 Dec 20.

Abstract

Mitochondria modify their function and morphology to satisfy the bioenergetic demand of the cells. Cancer cells take advantage of these features to sustain their metabolic, proliferative, metastatic, and survival necessities. Understanding the morphological changes to mitochondria in the different grades of triple-negative breast cancer (TNBC) could help to design new treatments. Consequently, this research explored mitochondrial morphology and the gene expression of some proteins related to mitochondrial dynamics, as well as proteins associated with oxidative and non-oxidative metabolism in metastatic and non-metastatic TNBC. We found that mitochondrial morphology and metabolism are different in metastatic and non-metastatic TNBC. In metastatic TNBC, there is overexpression of genes related to mitochondrial dynamics, fatty-acid metabolism, and glycolysis. These features are accompanied by a fused mitochondrial morphology. By comparison, in non-metastatic TNBC, there is a stress-associated mitochondrial morphology with hyperfragmented mitochondria, accompanied by the upregulated expression of genes associated with the biogenesis of mitochondria; both of which are characteristics related to the higher production of reactive oxygen species observed in this cell line. These differences between metastatic and non-metastatic TNBC should provide a better understanding of metastasis and contribute to the development of improved specific and personalized therapies for TNBC.

Keywords: cancer du sein triple négatif; cancer metabolism; metastasis; mitochondria morphology; morphologie des mitochondries; métabolisme du cancer; métastases; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Energy Metabolism
  • Epithelial-Mesenchymal Transition
  • Glycolysis*
  • Humans
  • Lipogenesis*
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Mitochondrial Dynamics*
  • Mitochondrial Proteins / genetics*
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism*
  • Transcriptome
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / secondary*
  • Tumor Cells, Cultured

Substances

  • Mitochondrial Proteins
  • Reactive Oxygen Species