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

Research output: Contribution to journalArticle

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 & 7 more Cheng Zhang, Heiko U. Käfferlein, Carsten Watzl, Saša Frank, Jörg Rahnenführer, Rosemarie Marchan, Jan G. Hengstler

Original languageEnglish
Pages (from-to)901-915
Number of pages15
JournalInternational Journal of Cancer
Volume145
Issue number4
Early online date17 Jan 2019
DOIs
Publication statusPublished - 15 Aug 2019

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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.

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