Unrevealed roles of extracellular enolase1 (ENO1) in promoting glycolysis and procancer activities in multiple myeloma via hypoxiainducible factor 1α.
Oncol Rep
; 50(5)2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37800625
ABSTRACT
The involvement of enolase1 (ENO1), intracellularly or extracellularly, has been implicated in cancer development. Moreover, anticancer activities of an ENO1targeting antibody has demonstrated the pathological roles of extracellular ENO1 (surface or secreted forms). However, although ENO1 was first identified as a glycolytic enzyme in the cytosol, to the best of our knowledge, extracellular ENO1 has not been implicated in glycolysis thus far. In the present study, the effects of extracellular ENO1 on glycolysis and other related procancer activities were investigated in multiple myeloma (MM) cells in vitro and in vivo. Knockdown of ENO1 expression reduced lactate production, cell viability, cell migration and surface ENO1 expression in MM cells. Notably, addition of extracellular ENO1 protein in cancer cell culture enhanced glycolytic activity, hypoxiainducible factor 1α (HIF1α) expression, glycolysisrelated gene (GRG) expression and procancer activities, such as cell migration, cell viability and tumorpromoting cytokine secretion. Consistently, these extracellular ENO1induced cellular effects were inhibited by an ENO1specific monoclonal antibody (mAb). In addition, extracellular ENO1mediated glycolysis, GRG expression and procancer activities were also reduced by HIF1α silencing. Lastly, administration of an ENO1 mAb reduced tumor growth and serum lactate levels in an MM xenograft model. These results suggested that extracellular ENO1 (surface or secreted forms) enhanced a HIF1αmediated glycolytic pathway, in addition to its already identified roles. Therefore, the results of the present study highlighted the therapeutic potential of ENO1specific antibodies in treating MM, possibly via glycolysis inhibition, and warrant further studies in other types of cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicólise
/
Mieloma Múltiplo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncol Rep
Ano de publicação:
2023
Tipo de documento:
Article