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.

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

CAPELLO, Michela;FERRI-BORGOGNO, SAMMY;RIGANTI, Chiara;CHATTARAGADA, MICHELLE SAMUEL;PRINCIPE, MOITZA;CAPPELLO, Paola;NOVELLI, Francesco
Last
2016-01-01

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.
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http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=6798&author-preview=58u
alpha-enolase, cancer metabolism, Warburg effect, cellular senescenc
Michela Capello; Sammy Ferri-Borgogno; Chiara Riganti; Michelle Samuel Chattaragada; Moitza Principe; Cecilia Roux; Weidong Zhou; Emanuel F. Petricoin; Paola Cappello; Francesco Novelli
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1542196
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