Fructose-1,6-bisphosphatase is a novel regulator of Wnt/β-Catenin pathway in breast cancer

Biomed Pharmacother. 2016 Dec;84:1144-1149. doi: 10.1016/j.biopha.2016.10.050. Epub 2016 Oct 22.

Abstract

Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is a tumor suppressor that frequently down-regulated in cancers, especially breast cancer. Here, we provide both supporting and contradicting evidences about the expression pattern and function of FBP1 in breast cancer. Data mining of Oncomine database showed that FBP1 is commonly up-regulated in tumor tissues compared with non-tumor tissues regardless of histological type. Analysis of a large-scale cohort derived from Kaplan-Meier Plotter showed that lower FBP1 expression associated with poor clinical outcome. Genetic silencing of FBP1 reduced aerobic glycolysis and the malignant potential of breast cancer cells. Gene set enrichment analysis (GSEA) of the expression profiles of breast cancer cells (n=59) revealed that cells exhibiting high expression of FBP1 had a lower activity of Wnt/β-Catenin pathway. FBP1 down-regulation enhanced the activity of Wnt/β-Catenin pathway and increased the level of its downstream targets, including c-Myc and MMP7. Collectively, our findings indicate that elevated FBP1 is a critical modulator in breast cancer progression by altering glucose metabolism and the activity of Wnt/β-Catenin pathway.

Keywords: -Catenin pathway; Breast cancer; FBP1; GSEA; Oncomine; Wnt/βbeta.

MeSH terms

  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Computational Biology
  • Databases, Genetic
  • Female
  • Fructose-Bisphosphatase / genetics
  • Fructose-Bisphosphatase / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glycolysis
  • Humans
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • Matrix Metalloproteinase 7 / genetics
  • Matrix Metalloproteinase 7 / metabolism
  • Neoplasm Invasiveness
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference
  • Time Factors
  • Transfection
  • Up-Regulation
  • Wnt Signaling Pathway*

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Fructose-Bisphosphatase
  • MMP7 protein, human
  • Matrix Metalloproteinase 7