ME1 promotes basal-like breast cancer progression and associates with poor prognosis

Sci Rep. 2018 Nov 13;8(1):16743. doi: 10.1038/s41598-018-35106-y.

Abstract

Basal-like breast cancer (BLBC) is associated with a poor clinical outcome due to the few treatment options and absence of effective targeted agents. Here, we show that malic enzyme 1 (ME1) is dramatically upregulated in BLBC due to ME1 copy number amplification. ME1 expression increases glucose uptake and lactate production, and reduces oxygen consumption, leading to aerobic glycolysis. ME1 expression promotes, whereas knockdown of ME1 expression suppresses tumorigenicity. In breast cancer patients, ME1 expression is positively correlated with large tumor size, high grade, poor survival, and chemotherapy resistance. Our study not only contributes to a new understanding of how metabolic reprogramming contributes to BLBC progression, but also provides a potential prognostic marker and therapeutic target for this challenging disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerobiosis
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Disease Progression*
  • Gene Dosage / genetics
  • Glycolysis
  • Humans
  • Malate Dehydrogenase / metabolism*
  • Prognosis
  • Tumor Hypoxia
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Malate Dehydrogenase
  • malate dehydrogenase (decarboxylating)