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

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.

• Authors: Cristina Cadenas, Sonja Vosbeck, Karolina Edlund, Katharina Grgas, Katrin Madjar, Birte Hellwig, Alshaimaa Adawy, Annika Glotzbach, Joanna D Stewart, Michaela S Lesjak, Dennis Franckenstein, Maren Claus, Heiko Hayen, Alexander Schriewer, Kathrin Gianmoena, Sonja Thaler, Marcus Schmidt, Patrick Micke, Fredrik Pontén, Adil Mardinoglu, Cheng Zhang, Heiko U Käfferlein, Carsten Watzl, Saša Frank, Jörg Rahnenführer, Rosemarie Marchan, Jan G Hengstler
• Journal: International journal of cancer (Int J Cancer) Vol. 145 Issue 4 Pg. 901-915 (08 15 2019) ISSN: 1097-0215 [Electronic] United States
• PMID: 30653260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Chemical References

• Lipids
• Lipoproteins, HDL
• LIPG protein, human
• Lipase

Topics

• Breast Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Disease Progression
• Disease-Free Survival
• Female
• Humans
• Lipase (metabolism)
• Lipid Metabolism (physiology)
• Lipids (physiology)
• Lipoproteins, HDL (metabolism)
• MCF-7 Cells
• Middle Aged
• Oxidative Stress (physiology)
• Up-Regulation (physiology)