Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia

被引：64

作者：

Al-Zoughbi, Wael ^{[1
]}

Pichler, Martin ^{[2
]}

Gorkiewicz, Gregor ^{[1
]}

Guertl-Lackner, Barbara ^{[1
]}

Haybaeck, Johannes ^{[1
]}

Jahn, Stephan W. ^{[1
]}

Lackner, Carolin ^{[1
]}

Liegl-Atzwanger, Bernadette ^{[1
]}

Popper, Helmut ^{[1
]}

Schauer, Silvia ^{[1
]}

Nusshold, Elisa ^{[1
]}

Kindt, Alida S. D. ^{[3
]}

Trajanoski, Zlatko ^{[3
]}

Speicher, Michael R. ^{[4
]}

Haemmerle, Guenther ^{[5
]}

Zimmermann, Robert ^{[5
]}

Zechner, Rudolf ^{[5
]}

Vesely, Paul W. ^{[1
,5
]}

Hoefler, Gerald ^{[1
]}

机构：

[1] Med Univ Graz, Inst Pathol, Graz, Austria

[2] Med Univ Graz, Div Oncol, Graz, Austria

[3] Med Univ Innsbruck, Div Bioinformat, Bioctr, A-6020 Innsbruck, Austria

[4] Med Univ Graz, Inst Human Genet, Graz, Austria

[5] Graz Univ, Inst Mol Biosci, Graz, Austria

来源：

ONCOTARGET | 2016年 / 7卷 / 23期

基金：

欧洲研究理事会; 奥地利科学基金会;

关键词：

adipose triglyceride lipase; cancer metabolism; lipolysis; diagnostic marker; WILMS-TUMOR; METABOLISM; LIPOLYSIS; FAT; REGIONS; ATGL; HETEROZYGOSITY; EXPRESSION; HALLMARK; TARGETS;

D O I：

10.18632/oncotarget.9418

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：33832 / 33840

页数：9

共 41 条

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