Seahorse-derived peptide suppresses invasive migration of HT1080 fibrosarcoma cells by competing with intracellular α-enolase for plasminogen binding and inhibiting uPA-mediated activation of plasminogen
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α-Enolase is a glycolytic enzyme and a surface receptor forplasminogen. α-Enolase-bound plasminogen promotes tumorcell invasion and cancer metastasis by activating plasmin andconsequently degrading the extracellular matrix degradation. Therefore, α-enolase and plasminogen are novel targets forcancer therapy. We found that the amino acid sequence of apeptide purified from enzymatic hydrolysates of seahorse hasstriking similarities to that of α-enolase. In this study, we reportthat this peptide competes with cellular α-enolase for plasminogenbinding and suppresses urokinase plasminogen activator(uPA)-mediated activation of plasminogen, which results indecreased invasive migration of HT1080 fibrosarcoma cells. Inaddition, the peptide treatment decreased the expression levelsof uPA compared to that of untreated controls. These resultsprovide new insight into the mechanism by which theseahorse-derived peptide suppresses invasive properties ofhuman cancer cells. Our findings suggest that this peptide couldemerge as a potential therapeutic agent for cancer.
Abstract
α-Enolase is a glycolytic enzyme and a surface receptor forplasminogen. α-Enolase-bound plasminogen promotes tumorcell invasion and cancer metastasis by activating plasmin andconsequently degrading the extracellular matrix degradation. Therefore, α-enolase and plasminogen are novel targets forcancer therapy. We found that the amino acid sequence of apeptide purified from enzymatic hydrolysates of seahorse hasstriking similarities to that of α-enolase. In this study, we reportthat this peptide competes with cellular α-enolase for plasminogenbinding and suppresses urokinase plasminogen activator(uPA)-mediated activation of plasminogen, which results indecreased invasive migration of HT1080 fibrosarcoma cells. Inaddition, the peptide treatment decreased the expression levelsof uPA compared to that of untreated controls. These resultsprovide new insight into the mechanism by which theseahorse-derived peptide suppresses invasive properties ofhuman cancer cells. Our findings suggest that this peptide couldemerge as a potential therapeutic agent for cancer.
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