Surface α-enolase promotes extracellular matrix degradation and tumor metastasis and represents a new therapeutic target.

In previous research, we found α-enolase to be inversely correlated with progression-free and overall survival in lung cancer patients and detected α-enolase on the surface of lung cancer cells. Based on these findings, we hypothesized that surface α-enolase has a significant role in cancer metastasis and tested this hypothesis in the current study. We found that α-enolase was co-immunoprecipitated with urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen in lung cancer cells and interacted with these proteins in a cell-free dot blotting assay, which can be interrupted by α-enolase-specific antibody. α-Enolase in lung cancer cells co-localized with these proteins and was present at the site of pericellular degradation of extracellular matrix components. Treatment with antibody against α-enolase in vitro suppressed cell-associated plasminogen and matrix metalloproteinase activation, collagen and gelatin degradation, and cell invasion. Examination of the effect of treatment with shRNA plasmids revealed that down regulation of α-enolase decreases extracellular matrix degradation by and the invasion capacity of lung cancer cells. Adoptive transfer of α-enolase-specific antibody to mice resulted in accumulation of antibody in subcutaneous tumor and inhibited the formation of tumor metastasis in lung and bone. This study demonstrated that surface α-enolase promotes extracellular matrix degradation and invasion of cancer cells and that targeting surface α-enolase is a promising approach to suppress tumor metastasis.
AuthorsKuan-Chung Hsiao, Neng-Yao Shih, Hsun-Lang Fang, Tze-Sing Huang, Ching-Chuan Kuo, Pei-Yi Chu, Yi-Mei Hung, Shao-Wen Chou, Yi-Yuan Yang, Gee-Chen Chang, Ko-Jiunn Liu
JournalPloS one (PLoS One) Vol. 8 Issue 7 Pg. e69354 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23894455 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Receptors, Urokinase Plasminogen Activator
  • Tumor Suppressor Proteins
  • Plasminogen
  • Urokinase-Type Plasminogen Activator
  • ENO1 protein, human
  • Phosphopyruvate Hydratase
  • Animals
  • Antibodies, Monoclonal (administration & dosage, pharmacology)
  • Biomarkers, Tumor (antagonists & inhibitors, metabolism)
  • Bone Neoplasms (drug therapy, secondary)
  • Cell Line, Tumor
  • Cell Membrane (metabolism)
  • Cell Movement
  • DNA-Binding Proteins (antagonists & inhibitors, metabolism)
  • Extracellular Matrix (metabolism)
  • Humans
  • Immunocompromised Host
  • Lung Neoplasms (metabolism, mortality, pathology)
  • Male
  • Mice
  • Neoplasm Metastasis
  • Neoplasms (metabolism, mortality, pathology)
  • Phosphopyruvate Hydratase (antagonists & inhibitors, metabolism)
  • Plasminogen (metabolism)
  • Protein Binding
  • Receptors, Urokinase Plasminogen Activator (metabolism)
  • Tumor Suppressor Proteins (antagonists & inhibitors, metabolism)
  • Urokinase-Type Plasminogen Activator (metabolism)
  • Xenograft Model Antitumor Assays

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