Quantitative proteome and lysine succinylome analyses provide insights into metabolic regulation in breast cancer

Breast Cancer. 2019 Jan;26(1):93-105. doi: 10.1007/s12282-018-0893-1. Epub 2018 Jul 18.

Abstract

Background: Breast cancer, the most common invasive cancer and cause of cancer-related death in women worldwide, is a multifactorial, complex disease, and many molecular players and mechanisms underlying the complexity of its clinical behavior remain unknown.

Methods: To explore the molecular features of breast cancer, quantitative proteome and succinylome analyses in breast cancer were extensively studied using quantitative proteomics techniques, anti-succinyl lysine antibody-based affinity enrichment, and high-resolution LC-MS/MS analysis.

Results: Our study is the first to detect the regulation of lysine succinylation in breast cancer progression. We identified a novel mechanism by which the pentose phosphate pathway and the endoplasmic reticulum protein processing pathway might be regulated via lysine succinylation in their core enzymes.

Conclusions: These results expand our understanding of tumorigenesis mechanisms and provide a basis for further characterization of the pathophysiological roles in breast cancer progression, laying a foundation for innovative and novel breast cancer drugs and therapies.

Keywords: Bioinformatics analysis; Breast cancer; Lysine succinylation; Proteomics; Quantitative analysis.

MeSH terms

  • Breast / pathology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Chromatography, High Pressure Liquid / methods
  • Computational Biology
  • Disease Progression
  • Female
  • Humans
  • Lysine / immunology
  • Lysine / metabolism*
  • Middle Aged
  • Protein Processing, Post-Translational
  • Proteome / metabolism*
  • Proteomics / methods*
  • Succinic Acid / immunology
  • Succinic Acid / metabolism*
  • Tandem Mass Spectrometry / methods

Substances

  • Proteome
  • Succinic Acid
  • Lysine