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Int J Cancer. 2019 Aug 15;145(4):901-915. doi: 10.1002/ijc.32138. Epub 2019 Feb 7.

LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer.

Author information

1
Department of Toxicology, Leibniz-Research Centre for Working Environment and Human Factors at the TU Dortmund (IfADo), Dortmund, Germany.
2
Department of Statistics, TU Dortmund University, Dortmund, Germany.
3
Department of Immunology, Leibniz-Research Centre for Working Environment and Human Factors at the TU Dortmund (IfADo), Dortmund, Germany.
4
Department of Analytical Chemistry, Institute of Inorganic and Analytical Chemistry, University of Münster, Münster, Germany.
5
European Center for Angioscience (ECAS), Medical Faculty Mannheim of the University of Heidelberg, Tridomus C, Mannheim, Germany.
6
Department of Obstetrics and Gynecology, University Hospital Mainz, Mainz, Germany.
7
Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
8
Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
9
Center of Toxicology, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr University Bochum, Bochum, Germany.
10
Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

Abstract

Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high-density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis-free survival in node-negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress-induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.

KEYWORDS:

LIPG; PLIN2; TXNRD1; breast cancer; endothelial lipase; lipid droplets; oxidative stress

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