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.
PLIN2
breast cancer
endothelial lipase
oxidative stress
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
Ruhr-Universität 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 4 901-915Subject 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