Targeting the Warburg effect in cancer cells through ENO1 knockdown rescues oxidative phosphorylation and induces growth arrest

Michela Capello, Sammy Ferri-Borgogno, Chiara Riganti, Michelle Samuel Chattaragada, Moitza Principe, Cecilia Roux, Weidong Zhou, Emanuel F. Petricoin, Paola Cappello, Francesco Novelli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

In the last 5 years, novel knowledge on tumor metabolism has been revealed with the identification of critical factors that fuel tumors. Alpha-enolase (ENO1) is commonly over-expressed in tumors and is a clinically relevant candidate molecular target for immunotherapy. Here, we silenced ENO1 in human cancer cell lines and evaluated its impact through proteomic, biochemical and functional approaches. ENO1 silencing increased reactive oxygen species that were mainly generated through the sorbitol and NADPH oxidase pathways, as well as autophagy and catabolic pathway adaptations, which together affect cancer cell growth and induce senescence. These findings represent the first comprehensive metabolic analysis following ENO1 silencing. Inhibition of ENO1, either alone, or in combination with other pathways which were perturbed by ENO1 silencing, opens novel avenues for future therapeutic approaches.

Original languageEnglish
Pages (from-to)5598-5612
Number of pages15
JournalOncotarget
Volume7
Issue number5
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • Alpha-enolase
  • Cancer metabolism
  • Cellular senescence
  • Warburg effect

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