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LIPG‐promoted lipid storage mediates adaptation to oxidative stress in breast cancer
Author(s) -
Cadenas Cristina,
Vosbeck Sonja,
Edlund Karolina,
Grgas Katharina,
Madjar Katrin,
Hellwig Birte,
Adawy Alshaimaa,
Glotzbach Annika,
Stewart Joanna D.,
Lesjak Michaela S.,
Franckenstein Dennis,
Claus Maren,
Hayen Heiko,
Schriewer Alexander,
Gianmoena Kathrin,
Thaler Sonja,
Schmidt Marcus,
Micke Patrick,
Pontén Fredrik,
Mardinoglu Adil,
Zhang Cheng,
Käfferlein Heiko U.,
Watzl Carsten,
Frank Saša,
Rahnenführer Jörg,
Marchan Rosemarie,
Hengstler Jan G.
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32138
Subject(s) - oxidative stress , downregulation and upregulation , cancer research , cancer , lipid droplet , biology , metastasis , medicine , microbiology and biotechnology , endocrinology , biochemistry , gene
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.