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PMID: 22050456 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Proteomic analysis reveals Warburg effect and anomalous metabolism of glutamine in pancreatic cancer cells.

Journal of proteome research ·Vol. 11 ·No. 2 ·2012-02-03 ·Pages 554-63

Zhou W, Capello M, Fredolini C, Racanicchi L, Piemonti L, Liotta LA, Novelli F, Petricoin EF

Abstract

In this present work, we characterized the proteomes of pancreatic ductal adenocarcinoma (PDAC) cell line PANC-1 and normal pancreatic duct cells by mass spectrometry using LTQ-Orbitrap and identified more than 1700 proteins from each sample. On the basis of the spectra count label-free quantification approach, we identified a large number of differentially expressed metabolic enzymes and proteins involved in cytoskeleton, cell adhesion, transport, transcription, translation, and cell proliferation as well. The data demonstrated that metabolic pathways were altered in PANC-1, consistent with the Warburg effect. In addition, the comparative MS analysis unveiled anomalous metabolism of glutamine, suggesting that glutamine was largely consumed as a nitrogen donor in nucleotide and amino acid biosynthesis in PANC-1. Our analysis provides a potentially comprehensive picture of metabolism in PANC-1, which may serve as the basis of new diagnostics and treatment of PDAC.

MeSH Terms
Carcinoma, Pancreatic Ductal/metabolism Case-Control Studies Cell Line, Tumor Chromatography, Liquid Down-Regulation Glutamine/metabolism Humans Metabolic Networks and Pathways Pancreatic Neoplasms/metabolism Proteome/analysis,metabolism Proteomics/methods Tandem Mass Spectrometry Up-Regulation
Chemicals
Proteome Glutamine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zhou Weidong
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia 20110, United States. wzhou@gmu.edu
Capello Michela
Fredolini Claudia
Racanicchi Leda
Piemonti Lorenzo
Liotta Lance A
Novelli Francesco
Petricoin Emanuel F
References (43)
43 references, click to expand
  1. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis.
    Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19345-50 PMID: 18032601
  2. Glutaminase: a hot spot for regulation of cancer cell metabolism?
    Oncotarget. 2010 Dec;1(8):734-40 PMID: 21234284
  3. Mechanism of cell adaptation: when and how do cancer cells develop chemoresistance?
    Cancer J. 2011 Mar-Apr;17(2):89-95 PMID: 21427552
  4. Cellular retinol binding protein-1 expression in endometrial hyperplasia and carcinoma: diagnostic and possible therapeutic implications.
    Mod Pathol. 2006 Jun;19(6):797-803 PMID: 16575402
  5. 150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic cell death.
    J Biol Chem. 1999 Mar 5;274(10):6397-404 PMID: 10037731
  6. Impact of tumor hypoxia and anemia on radiation therapy outcomes.
    Oncologist. 2002;7(6):492-508 PMID: 12490737
  7. Lysosomes as targets for cancer therapy.
    Cancer Res. 2005 Apr 15;65(8):2993-5 PMID: 15833821
  8. Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein.
    Mol Cell Proteomics. 2005 Sep;4(9):1265-72 PMID: 15958392
  9. Biology and management of pancreatic cancer.
    Gut. 2007 Aug;56(8):1134-52 PMID: 17625148
  10. Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry.
    Nat Methods. 2007 Mar;4(3):207-14 PMID: 17327847
  11. Cathepsin D in breast cancer: a tissue marker associated with metastasis.
    Eur J Cancer. 1992;28A(11):1780-3 PMID: 1389510
  12. Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer.
    Oncogene. 2010 Jan 21;29(3):313-24 PMID: 19881548
  13. A cystic fibrosis pancreatic adenocarcinoma cell line.
    Proc Natl Acad Sci U S A. 1990 May;87(10):4012-6 PMID: 1692630
  14. Metabolism and action of amino acid analog anti-cancer agents.
    Pharmacol Ther. 1990;46(2):243-71 PMID: 2108451
  15. Increased cytidine 5'-triphosphate synthetase activity in rat and human tumors.
    Cancer Res. 1980 Nov;40(11):3921-7 PMID: 7471043
  16. Understanding the Warburg effect: the metabolic requirements of cell proliferation.
    Science. 2009 May 22;324(5930):1029-33 PMID: 19460998
  17. Immunohistochemical localization of gamma-enolase in normal human tissues other than nervous and neuroendocrine tissues.
    Lab Invest. 1985 Mar;52(3):257-63 PMID: 3974199
  18. Mass spectrometry and protein analysis.
    Science. 2006 Apr 14;312(5771):212-7 PMID: 16614208
  19. The pancreatic cancer proteome - recent advances and future promise.
    Proteomics Clin Appl. 2007 Sep;1(9):1066-79 PMID: 21136758
  20. Proteomic profiling of pancreatic cancer for biomarker discovery.
    Mol Cell Proteomics. 2005 Apr;4(4):523-33 PMID: 15684406
  21. Lysosomes in cancer cells.
    J Clin Pathol Suppl (R Coll Pathol). 1974;7:43-50 PMID: 4598351
  22. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes.
    Science. 2010 Dec 3;330(6009):1340-4 PMID: 21127244
  23. Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.
    ASN Neuro. 2010 Jul 23;2(3):e00038 PMID: 20664705
  24. Structural and functional studies of the human selenium binding protein-1 and its involvement in hepatocellular carcinoma.
    Biochim Biophys Acta. 2011 Apr;1814(4):513-22 PMID: 21338716
  25. Glutamine addiction: a new therapeutic target in cancer.
    Trends Biochem Sci. 2010 Aug;35(8):427-33 PMID: 20570523
  26. Detection of point mutations in the Kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma.
    Ann Surg. 1993 Feb;217(2):138-43 PMID: 8439212
  27. Investigation and characterization of the duct cell-enriching process during serum-free suspension and monolayer culture using the human exocrine pancreas fraction.
    Pancreas. 2009 Jan;38(1):36-48 PMID: 18665014
  28. The expression of selenium-binding protein 1 is decreased in uterine leiomyoma.
    Diagn Pathol. 2010 Dec 09;5:80 PMID: 21143902
  29. Proteomics studies of pancreatic cancer.
    Proteomics Clin Appl. 2007;1(12):1582-1591 PMID: 18633454
  30. Pancreatic cancer: proteomic approaches to a challenging disease.
    Pancreatology. 2009;9(5):567-76 PMID: 19657212
  31. Epigenetics and epigenetic alterations in pancreatic cancer.
    Int J Clin Exp Pathol. 2009;2(4):310-26 PMID: 19158989
  32. Mass spectrometry in high-throughput proteomics: ready for the big time.
    Nat Methods. 2010 Sep;7(9):681-5 PMID: 20805795
  33. A model for random sampling and estimation of relative protein abundance in shotgun proteomics.
    Anal Chem. 2004 Jul 15;76(14):4193-201 PMID: 15253663
  34. Glycolysis inhibition for anticancer treatment.
    Oncogene. 2006 Aug 7;25(34):4633-46 PMID: 16892078
  35. Otto Warburg's contributions to current concepts of cancer metabolism.
    Nat Rev Cancer. 2011 May;11(5):325-37 PMID: 21508971
  36. Proteomic analysis of pancreatic ductal adenocarcinoma cells reveals metabolic alterations.
    J Proteome Res. 2011 Apr 1;10(4):1944-52 PMID: 21309613
  37. An essential role for p300/CBP in the cellular response to hypoxia.
    Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12969-73 PMID: 8917528
  38. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.
    Science. 2001 Apr 20;292(5516):468-72 PMID: 11292861
  39. A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase.
    EMBO J. 1991 Dec;10(13):4267-77 PMID: 1756734
  40. The biological impact of mass-spectrometry-based proteomics.
    Nature. 2007 Dec 13;450(7172):991-1000 PMID: 18075578
  41. On respiratory impairment in cancer cells.
    Science. 1956 Aug 10;124(3215):269-70 PMID: 13351639
  42. Establishment of a continuous tumor-cell line (panc-1) from a human carcinoma of the exocrine pancreas.
    Int J Cancer. 1975 May 15;15(5):741-7 PMID: 1140870
  43. Lysosomes and autophagy in cell death control.
    Nat Rev Cancer. 2005 Nov;5(11):886-97 PMID: 16239905
Article Info
Journal
Journal of proteome research
Abbr.
J Proteome Res
ISSN
1535-3907
DOI
10.1021/pr2009274
Email
wzhou@gmu.edu
Published
2012-02-03
Epub
2011-00-17
Pages
554-63
Language
English
Region
United States
NLM ID
101128775
PMCID
PMC5564318
Subset
IM
Grants
NCI NIH HHS · R21 CA125698 · United States
NEI NIH HHS · R21 EY018942 · United States
NCI NIH HHS · R33 CA157403 · United States
External Links
PubMed source DOI: 10.1021/pr2009274 PMC Full Text View journal details
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