Surface α-Enolase Promotes Extracellular Matrix Degradation and Tumor Metastasis and Represents a New Therapeutic Target

Kuan 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

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Abstract

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.

Original languageEnglish
Article numbere69354
JournalPLoS One
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 19 2013

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hsiao, K. C., Shih, N. Y., Fang, H. L., Huang, T. S., Kuo, C. C., Chu, P. Y., Hung, Y. M., Chou, S. W., Yang, Y. Y., Chang, G. C., & Liu, K. J. (2013). Surface α-Enolase Promotes Extracellular Matrix Degradation and Tumor Metastasis and Represents a New Therapeutic Target. PLoS One, 8(7), [e69354]. https://doi.org/10.1371/journal.pone.0069354