645394.pdf

For Peer Review
Fatty acid synthase is a metabolic marker of cell
proliferation rather than malignancy in ovarian cancer and
its precursor cells
Journal: International Journal of Cancer
Manuscript ID: IJC-14-1414.R1
Wiley - Manuscript type: Cancer Cell Biology
Date Submitted by the Author: n/a
Complete List of Authors: Veigel, Daniel; Medical University of Vienna, Dept. of Medicine I, Dept. of
Medicine I, Signaling Networks Program, Div. of Oncology
Wagner, Renate; Medical University of Vienna, Dept. of Medicine I, Dept. of
Medicine I, Signaling Networks Program, Div. of Oncology
Stübiger, Gerald; Medical University of Vienna, Department of Vascular
Biology and Thrombosis Research, Center of Physiology and Pharmacology
Wuczkowski, Michael; Medical University of Vienna, Department of Vascular
Biology and Thrombosis Research, Center of Physiology and Pharmacology
Filipits, Martin; Medical University of Vienna, Institute of Cancer Research,
Department of Medicine I
Horvat, Reinhard; Medical University of Vienna, Clinical Institute of
Pathology
Benhamú, Bellinda; Universidad Complutense de Madrid, Departamento de
Química Orgánica I, Facultad de Ciencias Químicas
López-Rodríguez, María Luz; Universidad Complutense de Madrid,
Departamento de Química Orgánica I, Facultad de Ciencias Químicas
Leisser, Asha; Medical University of Vienna, Dept. of Medicine I, Dept. of
Medicine I, Signaling Networks Program, Div. of Oncology
Valent, Peter; Medical University of Vienna, Dept. of Internal Medicine I,
Div. of Hematology and Hemostaseology
Grusch, Michael; Medical University of Vienna, Institute of Cancer
Research, Department of Medicine I
Hegardt, Fausto; Universitat de Barcelona, Department of Biochemistry
and Molecular Biology
García, Jordi; Universitat de Barcelona, Department of Organic Chemistry
Serra, Dolors; Universitat de Barcelona, Department of Biochemistry and
Molecular Biology
Auersperg, Nelly; University of British Columbia, Department of Obstetrics
and Gynecology
Colomer, Ramón; Hospital Universitario La Princesa and Spanish National
Cancer Research Center (CNIO), Department of Medical Oncology
Grunt, Thomas; Medical University of Vienna, Dept. of Internal Medicine I,
Signaling Networks Program, Div. of Oncology
Key Words:
fallopian tube secretory epithelial cells, fatty acid synthase, ovarian cancer,
ovarian surface epithelial cells, senescence
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International Journal of Cancer

For Peer Review
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Fatty acid synthase is a metabolic marker of cell proliferation rather than
malignancy in ovarian cancer and its precursor cells
Daniel Veigel1,2*, Renate Wagner1,2*, Gerald Stübiger2,3, Michael Wuczkowski3, Martin Filipits2,4,
Reinhard Horvat5, Bellinda Benhamú6, María Luz López-Rodríguez6, Asha Leisser1,13, Peter Valent2,7,13,
Michael Grusch2,4, Fausto G. Hegardt8,9, Jordi García9,10, Dolors Serra8,9, Nelly Auersperg11, Ramón
Colomer12, Thomas W. Grunt1,2,13
1Signaling Networks Program, Division of Oncology, Department of Medicine I, Medical University
Vienna, Vienna, Austria
2Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria
3Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology,
Medical University Vienna, Vienna, Austria
4Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna,
Austria
5Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
6Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense de
Madrid, Madrid, Spain
7Division of Hematology and Hemostaseology, Department of Medicine I, Medical University Vienna,
Vienna, Austria
8Department of Biochemistry and Molecular Biology, Facultat de Farmàcia, Universitat de Barcelona,
Barcelona, Spain
9Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona and CIBERobn
Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain
10Department of Organic Chemistry, Facultat de Química, Universitat de Barcelona, Barcelona, Spain
11Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
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12Department of Medical Oncology, Hospital Universitario La Princesa and Spanish National Cancer
Research Center (CNIO), Clinical Research Program, Madrid, Spain
13Ludwig Boltzmann Cluster Oncology, Vienna, Austria
*D.V. and R.W. contributed equally to this work.
Correspondence to: Thomas W. Grunt, Division of Oncology, Department of Medicine I,
Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18 – 20, A-1090
Vienna, Austria, Tel.: [phone], -44300, Fax: [phone], E-mail:
[e-mail]
Short title: FASN – a growth marker independent of cancer
Key words: Fallopian tube secretory epithelial cells, fatty acid synthase, ovarian cancer, ovarian
surface epithelial cells, senescence
Abbreviations: CE: cholesterol ester; DAG: diacylglycerol; FASN: fatty acid synthase; FCS: fetal calf
serum; OC: ovarian cancer; OSE: ovarian surface epithelial cells; PARP: poly (ADP-ribose) polymerase;
PE: phosphatidylethanolamine; PC: phosphatidylcholine; PI: phosphatidylinositol; PL: phospholipid;
PS: phosphatidylserine; SM: sphingomyelin; TAG: triacylglycerol; TLC thin-layer chromatography
Manuscript Category: Research Article – Cancer Cell Biology
Word count Abstract: 240
Word count Main Text: 4510
Supplementary information accompanies the paper.
What’s new?
Fatty acid synthase (FASN) has been regarded as marker of malignancy and as cancer drug target.
Being overexpressed in cancer it regulates oncogenic de-novo-lipogenesis. There is general
agreement that normal cells are FASN-negative. We now demonstrate that FASN is overexpressed in
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the ovarian system when cells reveal high growth rates, which correlates with distinctive lipid
profiles, irrespective of their state of malignancy/differentiation/senescence. Thus, FASN represents
a metabolic marker of ovarian cell proliferation rather than of cancer.
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