title: Cancer abolishes the tissue type-specific differences in the phenotype of energetic metabolism.
abstract: Nowadays, cellular bioenergetics has become a central issue of investigation in cancer biology. Recently, the metabolic activity of the cancer cell has been shown to correlate with a proteomic index that informs of the relative mitochondrial activity of the cell. Within this new field of investigation, we report herein the production and characterization of high-affinity monoclonal antibodies against proteins of the "bioenergetic signature" of the cell. The use of recombinant proteins and antibodies against the mitochondrial beta-F1-ATPase and Hsp60 proteins and the enzymes of the glycolytic pathway glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase M2 in quantitative assays provide, for the first time, the actual amount of these proteins in normal and tumor surgical specimens of breast, lung, and esophagus. The application of this methodology affords a straightforward proteomic signature that quantifies the variable energetic demand of human tissues. Furthermore, the results show an unanticipated finding: tumors from different tissues and/or histological types have the same proteomic signature of energetic metabolism. Therefore, the results indicate that cancer abolishes the tissue-specific differences in the bioenergetic phenotype of mitochondria. Overall, the results support that energetic metabolism represents an additional hallmark of the phenotype of the cancer cell and a promising target for the treatment of diverse neoplasias.
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, C.S.I.C.-U.A.M., Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 28049 Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Acebo
authors.forename: Daniel
authors.initials: D
authors.lastname: Giner
authors.forename: Piedad
authors.initials: P
authors.lastname: Calvo
authors.forename: Amaya
authors.initials: A
authors.lastname: Blanco-Rivero
authors.forename: Alvaro D
authors.initials: AD
authors.lastname: Ortega
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Fernández
authors.forename: Giovanna
authors.initials: G
authors.lastname: Roncador
authors.forename: Edgar
authors.initials: E
authors.lastname: Fernández-Malavé
authors.forename: Margarita
authors.initials: M
authors.lastname: Chamorro
authors.forename: José M
authors.initials: JM
authors.lastname: Cuezva
references.citation: Science. 2006 Jun 16;312(5780):1650-3
references.pmid: 16728594
references.citation: Nature. 2008 Mar 13;452(7184):181-6
references.pmid: 18337815
references.citation: Nature. 2007 Jun 7;447(7145):741-4
references.pmid: 17554312
references.citation: Nature. 1976 Jun 24;261(5562):702-5
references.pmid: 934318
references.citation: Carcinogenesis. 2008 Nov;29(11):2053-61
references.pmid: 18687667
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5992-7
references.pmid: 15840712
references.citation: Int J Cancer. 2008 Jul 15;123(2):476-483
references.pmid: 18452174
references.citation: Cancer Res. 2002 Nov 15;62(22):6674-81
references.pmid: 12438266
references.citation: Nat Genet. 2008 May;40(5):499-507
references.pmid: 18443585
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Carcinogenesis. 2006 May;27(5):925-35
references.pmid: 16361271
references.citation: Int J Colorectal Dis. 2008 Dec;23(12):1223-32
references.pmid: 18769884
references.citation: J Biol Chem. 2006 Jan 13;281(2):977-81
references.pmid: 16263703
references.citation: Cancer Res. 2005 Apr 15;65(8):3162-70
references.pmid: 15833846
references.citation: Curr Opin Biotechnol. 2006 Aug;17(4):415-21
references.pmid: 16837184
references.citation: Cancer Res. 2002 Jul 15;62(14):3909-13
references.pmid: 12124317
references.citation: PLoS One. 2006 Dec 20;1:e107
references.pmid: 17205111
references.citation: Cancer Cell. 2007 Jan;11(1):37-51
references.pmid: 17222789
references.citation: Nature. 2008 Mar 13;452(7184):230-3
references.pmid: 18337823
references.citation: Biochem J. 2004 Feb 15;378(Pt 1):17-20
references.pmid: 14683524
references.citation: Novartis Found Symp. 2001;240:251-60; discussion 260-4
references.pmid: 11727934
references.citation: Mol Cell. 1998 Feb;1(3):327-36
references.pmid: 9660917
references.citation: Cell Metab. 2008 Jan;7(1):11-20
references.pmid: 18177721
references.citation: Carcinogenesis. 2004 Jul;25(7):1157-63
references.pmid: 14963017
references.citation: J Natl Cancer Inst. 2006 Oct 18;98(20):1462-73
references.pmid: 17047195
references.citation: Trends Cell Biol. 2008 Apr;18(4):165-73
references.pmid: 18296052
references.citation: Cancer Res. 2006 Sep 15;66(18):8927-30
references.pmid: 16982728
references.citation: Cancer Res. 2007 Oct 1;67(19):9013-7
references.pmid: 17909002
references.citation: J Bioenerg Biomembr. 2007 Jun;39(3):259-65
references.pmid: 17712532
references.citation: Cell. 2003 Nov 26;115(5):629-40
references.pmid: 14651853
references.citation: J Clin Invest. 2007 Mar;117(3):719-29
references.pmid: 17318262
references.citation: Cancer Res. 2007 Apr 1;67(7):3364-70
references.pmid: 17409446
references.citation: Carcinogenesis. 2005 Dec;26(12):2095-104
references.pmid: 16033770