These authors contributed equally to this study.
Increased anaerobic metabolism is a distinctive signature in a colorectal cancer cellular model of resistance to antiepidermal growth factor receptor antibody
Article first published online: 24 JAN 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Volume 13, Issue 5, pages 866–877, March 2013
How to Cite
Monteleone, F., Rosa, R., Vitale, M., D'Ambrosio, C., Succoio, M., Formisano, L., Nappi, L., Romano, M. F., Scaloni, A., Tortora, G., Bianco, R. and Zambrano, N. (2013), Increased anaerobic metabolism is a distinctive signature in a colorectal cancer cellular model of resistance to antiepidermal growth factor receptor antibody. Proteomics, 13: 866–877. doi: 10.1002/pmic.201200303
Colour Online: See the article online to view Fig. 1 in colour.
- Issue published online: 8 MAR 2013
- Article first published online: 24 JAN 2013
- Accepted manuscript online: 26 DEC 2012 08:46AM EST
- Manuscript Accepted: 14 NOV 2012
- Manuscript Revised: 12 OCT 2012
- Manuscript Received: 20 JUL 2012
- Ministero dell'Università e della Ricerca Scientifica (MIUR)
- Associazione Italiana per la Ricerca sul Cancro (AIRC). Grant Numbers: PS 126-Ind, 2011–2014, MFAG-11473, MIUR_PRIN2008_CCPKRP_002, MIUR_FIRB2008_RBNE08YFN3_003
- Finanziamenti per l'Avvio di Ricerche Originali (FARO). Grant Numbers: AIRC_IG-11930, MIUR_PRIN 2009×23L78_005
- 2D DIGE;
- Biological drugs;
- Warburg effect
Cetuximab is a chimeric antibody approved for the treatment of metastatic colorectal cancer that selectively targets epidermal growth factor receptor (EGFR) signaling. Treatment efficacy with this drug is often impaired by acquired resistance and poor information has been accumulated on the mechanisms underlying such a phenomenon. By taking advantage of a syngenic cellular system of sensitivity and acquired resistance to anti-EGFR therapy in the colorectal carcinoma GEO cell line, we profiled protein expression differences between Cetuximab-sensitive and -resistant cells. Combined 2D DIGE and MS analyses revealed a main proteomic signature resulting from selective deregulation of various metabolic enzymes, including glucose-6-phosphate dehydrogenase, transketolase, lactate dehydrogenase B, and pyruvate dehydrogenase E1, which was also confirmed by Western blotting experiments. Lactate dehydrogenase B downregulation has been already related to an increased anaerobic utilization of glucose by tumor cells; accordingly, we verified that Cetuximab-resistant cells have a significantly higher production of lactate. Resistant cells also showed decreased nicotinamide adenine dinucleotide phosphate (NADPH) levels. Observed protein deregulations were not related to functional alterations of the hypoxia-inducible factor 1-associated pathways. Our data demonstrate that increased anaerobic metabolism is a prominent feature observed in the GEO syngenic model of acquired resistance to anti-EGFR therapy in colorectal cancer.