LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer
Journal article, 2019

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.

oxidative stress

endothelial lipase

PLIN2

breast cancer

lipid droplets

TXNRD1

LIPG

Author

Cristina Cadenas

Technische Universität Dortmund

Sonja Vosbeck

Technische Universität Dortmund

Karolina Edlund

Technische Universität Dortmund

Katharina Grgas

Technische Universität Dortmund

Katrin Madjar

Technische Universität Dortmund

Birte Hellwig

Technische Universität Dortmund

Alshaimaa Adawy

Technische Universität Dortmund

Annika Glotzbach

Technische Universität Dortmund

Joanna D. Stewart

Technische Universität Dortmund

University of Southampton

Michaela S. Lesjak

Technische Universität Dortmund

Dennis Franckenstein

Technische Universität Dortmund

Maren Claus

Technische Universität Dortmund

Heiko Hayen

University of Münster

Alexander Schriewer

University of Münster

Kathrin Gianmoena

Technische Universität Dortmund

Sonja Thaler

Heidelberg University

Marcus Schmidt

Univ Hosp Mainz

Patrick Micke

Uppsala University

Fredrik Ponten

Uppsala University

Adil Mardinoglu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

C. Zhang

Royal Institute of Technology (KTH)

Heiko U. Kaefferlein

Inst Ruhr Univ Bochum

Carsten Watzl

Technische Universität Dortmund

Sasa Frank

Medical University of Graz

Jorg Rahnenfuehrer

Technische Universität Dortmund

Rosemarie Marchan

Technische Universität Dortmund

Jan G. Hengstler

Technische Universität Dortmund

International Journal of Cancer

0020-7136 (ISSN) 1097-0215 (eISSN)

Vol. 145 4 901-915

Subject Categories

Cell and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Cancer and Oncology

DOI

10.1002/ijc.32138

PubMed

30653260

More information

Latest update

12/6/2019