Oncotarget

Research Papers:

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 and Francesco Novelli _

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Oncotarget. 2016; 7:5598-5612. https://doi.org/10.18632/oncotarget.6798

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Abstract

Michela Capello1,2,7,*, Sammy Ferri-Borgogno1,2,8,*, Chiara Riganti3, Michelle Samuel Chattaragada1,2, Moitza Principe1,2, Cecilia Roux1,2, Weidong Zhou4, Emanuel F. Petricoin4, Paola Cappello1,2,5, Francesco Novelli1,2,5,6

1Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin 10126, Italy

2Center for Experimental Research and Medical Studies, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy

3Department of Oncology, University of Turin, Turin 10126, Italy

4Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA

5Molecular Biotechnology Center, Turin 10126, Italy

6Immunogenetics and Transplantation Biology Service, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy

7Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

8Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

*These authors contributed equally to this work

Correspondence to:

Francesco Novelli, e-mail: franco.novelli@unito.it

Keywords: alpha-enolase, cancer metabolism, Warburg effect, cellular senescence

Received: July 18, 2015     Accepted: December 05, 2015     Published: December 30, 2015

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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