title: Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia.
abstract: Metabolic reprogramming is a hallmark of cancer. Understanding cancer metabolism is instrumental to devise innovative therapeutic approaches. Anabolic metabolism, including the induction of lipogenic enzymes, is a key feature of proliferating cells. Here, we report a novel tumor suppressive function for adipose triglyceride lipase (ATGL), the rate limiting enzyme in the triglyceride hydrolysis cascade.In immunohistochemical analysis, non-small cell lung cancers, pancreatic adenocarcinoma as well as leiomyosarcoma showed significantly reduced levels of ATGL protein compared to corresponding normal tissues. The ATGL gene was frequently deleted in various forms of cancers. Low levels of ATGL mRNA correlated with significantly reduced survival in patients with ovarian, breast, gastric and non-small cell lung cancers. Remarkably, pulmonary neoplasia including invasive adenocarcinoma developed spontaneously in mice lacking ATGL pointing to an important role for this lipase in controlling tumor development.Loss of ATGL, as detected in several forms of human cancer, induces spontaneous development of pulmonary neoplasia in a mouse model. Our results, therefore, suggest a novel tumor suppressor function for ATGL and contribute to the understanding of cancer metabolism. We propose to evaluate loss of ATGL protein expression for the diagnosis of malignant tumors. Finally, modulation of the lipolytic pathway may represent a novel therapeutic approach in the treatment of human cancer.
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Wael
authors.initials: W
authors.lastname: Al-Zoughbi
authors.affiliation: Division of Oncology, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Gorkiewicz
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Guertl-Lackner
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Haybaeck
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Jahn
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Carolin
authors.initials: C
authors.lastname: Lackner
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Liegl-Atzwanger
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Popper
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schauer
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nusshold
authors.affiliation: Biocenter, Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Alida S D
authors.initials: AS
authors.lastname: Kindt
authors.affiliation: Biocenter, Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
authors.affiliation: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Speicher
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Guenther
authors.initials: G
authors.lastname: Haemmerle
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.|Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Vesely
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019295:Computational Biology; D057225:Data Mining; D030541:Databases, Genetic; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008049:Lipase / Q000032:analysis* / Q000172:deficiency* / Q000235:genetics; D008066:Lipolysis; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D000217:Acyltransferases
chemical_list: D014408:Biomarkers, Tumor; D008049:Lipase; C494794:PNPLA2 protein, human; D000217:Acyltransferases; C494445:PNPLA2 protein, mouse
keywords: adipose triglyceride lipase; cancer metabolism; diagnostic marker; lipolysis