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

In previous research, we found alpha-enolase to be inversely correlated with progression-free and overall survival in lung cancer patients and detected alpha-enolase on the surface of lung cancer cells. Based on these findings, we hypothesized that surface alpha-enolase has a significant role in cancer metastasis and tested this hypothesis in the current study. We found that alpha-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 alpha-enolase-specific antibody. alpha-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 alpha-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 alpha-enolase decreases extracellular matrix degradation by and the invasion capacity of lung cancer cells. Adoptive transfer of alpha-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 alpha-enolase promotes extracellular matrix degradation and invasion of cancer cells and that targeting surface alpha-enolase is a promising approach to suppress tumor metastasis.