title: 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.
authors.affiliation: Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kuan-Chung
authors.initials: KC
authors.lastname: Hsiao
authors.forename: Neng-Yao
authors.initials: NY
authors.lastname: Shih
authors.forename: Hsun-Lang
authors.initials: HL
authors.lastname: Fang
authors.forename: Tze-Sing
authors.initials: TS
authors.lastname: Huang
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Kuo
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Chu
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Hung
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Chou
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Yang
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.forename: Ko-Jiunn
authors.initials: KJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D016867:Immunocompromised Host; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D055293:Receptors, Urokinase Plasminogen Activator; D025521:Tumor Suppressor Proteins; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase
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