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

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.

Defining the Na+/H+ exchanger NHE1 interactome in triple-negative breast cancer cells

“…α-enolase is a cytosolic glycolytic enzyme and oxidative stress protein. Its expression is elevated in many tumours, including those of the breast, where it is also found on the cell surface [46,47]. The NHE1-α-enolase complex was confirmed by both affinity chromatography and co-immunoprecipitation.…”

MiR-886-5p Inhibition Inhibits Growth and Induces Apoptosis of MCF7 Cells

“…It is well known that degradation of the extracellular matrix surrounding tumors is the most common feature for tumor cell invasion into surrounding tissues and early metastasis. Certain MMPs are found secreted by invading tumor cells which can degrade the extracellular matrix (Hsiao, 2013;Guo et al, 2013). Thus, expression levels of these MMPs effectively reflect the DOI:http://dx.doi.org/10.7314/APJCP.2014.15.4.1511 Inhibitor Inhibits Growth and Induces Apoptosis of MCF7 Cells aggressiveness of tumor cells and are associated with poor prognosis in various cancers.…”

STIM1/ORAI1-mediated Ca2+ Influx Regulates Enolase-1 Exteriorization

“…However, under stimulatory conditions, it can be translocated to the cell surface where it interacts with PLG and thus participates in the regulation of pericellular proteolysis, allowing cells to invade tissue (13)(14)(15). This fact can explain the positive correlation between high levels of ENO-1 present on the cell surface of cancer cells (16 -19) and their increased invasive potential (20,21). In agreement with this notion, patients with non-small cell lung cancer whose tumors expressed high levels of cell surface bound ENO-1 were found to have a poor survival outcome (22).…”