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Oncotarget. 2016 Feb 2;7(5):5598-612. doi: 10.18632/oncotarget.6798.

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

Author information

1
Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin 10126, Italy.
2
Center for Experimental Research and Medical Studies, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.
3
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
4
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
5
Department of Oncology, University of Turin, Turin 10126, Italy.
6
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.
7
Molecular Biotechnology Center, Turin 10126, Italy.
8
Immunogenetics and Transplantation Biology Service, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.

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.

KEYWORDS:

Warburg effect; alpha-enolase; cancer metabolism; cellular senescence

PMID:
26734996
PMCID:
PMC4868708
DOI:
10.18632/oncotarget.6798
[Indexed for MEDLINE]
Free PMC Article

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