title: Targeting the Warburg effect in cancer cells through ENO1 knockdown rescues oxidative phosphorylation and induces growth arrest.
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.
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin 10126, Italy.|Center for Experimental Research and Medical Studies, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.|Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Capello
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin 10126, Italy.|Center for Experimental Research and Medical Studies, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.|Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sammy
authors.initials: S
authors.lastname: Ferri-Borgogno
authors.affiliation: Department of Oncology, University of Turin, Turin 10126, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Riganti
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin 10126, Italy.|Center for Experimental Research and Medical Studies, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.
authors.forename: Michelle Samuel
authors.initials: MS
authors.lastname: Chattaragada
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin 10126, Italy.|Center for Experimental Research and Medical Studies, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.
authors.forename: Moitza
authors.initials: M
authors.lastname: Principe
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin 10126, Italy.|Center for Experimental Research and Medical Studies, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Roux
authors.affiliation: Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin 10126, Italy.|Center for Experimental Research and Medical Studies, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.|Molecular Biotechnology Center, Turin 10126, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cappello
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin 10126, Italy.|Center for Experimental Research and Medical Studies, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.|Molecular Biotechnology Center, Turin 10126, Italy.|Immunogenetics and Transplantation Biology Service, University Hospital Città della Salute e della Scienza di Torino, Torino 10126, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D010085:Oxidative Phosphorylation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000037:antagonists & inhibitors* / Q000235:genetics; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase
keywords: Warburg effect; alpha-enolase; cancer metabolism; cellular senescence