Abstract 1889: Can the moonlighting glycolytic enzyme α-enolase be a therapeutic target in pancreatic cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 8_Supplement; p. 1889
• Main Authors: Capello, Michela, Principe, Moitza, Chattaragada, Michelle Samuel, Riganti, Chiara, Zhou, Weidong, Ferri-Borgogno, Sammy, Rolla, Simona, Liotta, Lance, Petricoin, Emanuel, Cappello, Paola, Novelli, Francesco
• Format: Journal Article
• Language: English
• Published: 15.04.2013
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-1889

Abstract Aberrant metabolism together with invasion and metastasis are hallmarks of cancer. This is particularly true for pancreatic ductal adenocarcinoma (PDAC), characterized by rapid progression, invasiveness and resistance to treatments. We have previously described α-enolase (ENOA) as a PDAC-associated antigen. It is a moonlighting protein that works both as a key metabolic enzyme and as a membrane plasminogen receptor. In order to clarify its multifunctional role in pancreatic tumorigenesis we investigated the effect of ENOA knockdown in PDAC cells. Protein expression alterations following ENOA knockdown in the human PDAC cell line CFPAC-1 were revealed by LC-MS/MS analysis. On the basis of a spectra count label-free quantitation approach a large number of proteins mainly involved in cell adhesion, metabolism and proliferation were found to be differentially expressed in ENOA silenced cells compared to the control. After ENOA silencing, PDAC cells displayed a delay in proliferation and decreased survival and colony formation capabilities, even if the pyruvate production was not affected. The growth inhibition was partially due to an increased concentration of intracellular reactive oxygen species (ROS) mainly generated through the sorbitol and NADPH oxidase pathways. Moreover in ENOA silenced cells, the in vitro plasminogen-driven invasion was abolished and the number of lung tumor masses was significantly reduced in SCID-beige mice injected with ENOA silenced cells compared to mice injected with control cells. These effects are under further confirmation in other PDAC cell lines. All together, these findings propose ENOA as a promising target for developing new therapies in pancreatic cancer management. Citation Format: Michela Capello, Moitza Principe, Michelle Samuel Chattaragada, Chiara Riganti, Weidong Zhou, Sammy Ferri-Borgogno, Simona Rolla, Lance Liotta, Emanuel Petricoin, Paola Cappello, Francesco Novelli. Can the moonlighting glycolytic enzyme α-enolase be a therapeutic target in pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1889. doi:10.1158/1538-7445.AM2013-1889