FOXM1-LDHA signaling promoted gastric cancer glycolytic phenotype and progression

Int J Clin Exp Pathol. 2015 Jun 1;8(6):6756-63. eCollection 2015.

Abstract

The oncogenic transcription factor forkhead box protein M1 (FOXM1) plays critical roles in gastric cancer (GC) development and progression. However, the underlying mechanisms has not fully demonstrated. Lactate dehydrogenase A (LDHA) is widely overexpressed in a series of cancers and is one of the two subunits of Lactate dehydrogenase (LDH), which is the key glycolytic enzyme and catalyzes the interconversion of pyruvate and lactate. In this study, we characterized the regulation of aerobic glycolysis by FOXM1 via transactivation of LDHA in GC. We found that LDHA was overexpressed GC cells, and the expression of LDHA was transcriptionally regulated by FOXM1. Furthermore, FOXM1 regulated GC cells glycolytic phenotype, proliferation, migration and invasion via LDHA. Thus, FOXM1-LDHA signaling functioned as a stimulator of glycolysis and promoted GC progression.

Keywords: FOXM1; LDHA; gastric cancer; glycolysis1; progression.

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Enzyme Activation
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glycolysis*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / genetics
  • L-Lactate Dehydrogenase / metabolism*
  • Lactate Dehydrogenase 5
  • Neoplasm Invasiveness
  • Phenotype
  • Promoter Regions, Genetic
  • RNA Interference
  • Signal Transduction*
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection
  • Up-Regulation

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Isoenzymes
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5