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

TY - JOUR

T1 - LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer

AU - Cadenas, Cristina

AU - Vosbeck, Sonja

AU - Edlund, Karolina

AU - Grgas, Katharina

AU - Madjar, Katrin

AU - Hellwig, Birte

AU - Adawy, Alshaimaa

AU - Glotzbach, Annika

AU - Stewart, Joanna D.

AU - Lesjak, Michaela S.

AU - Franckenstein, Dennis

AU - Claus, Maren

AU - Hayen, Heiko

AU - Schriewer, Alexander

AU - Gianmoena, Kathrin

AU - Thaler, Sonja

AU - Schmidt, Marcus

AU - Micke, Patrick

AU - Pontén, Fredrik

AU - Mardinoglu, Adil

AU - Zhang, Cheng

AU - Käfferlein, Heiko U.

AU - Watzl, Carsten

AU - Frank, Saša

AU - Rahnenführer, Jörg

AU - Marchan, Rosemarie

AU - Hengstler, Jan G.

PY - 2019/8/15

Y1 - 2019/8/15

N2 - 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.

AB - 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.

KW - breast cancer

KW - endothelial lipase

KW - LIPG

KW - lipid droplets

KW - oxidative stress

KW - PLIN2

KW - TXNRD1

UR - https://www.scopus.com/pages/publications/85061234180

U2 - 10.1002/ijc.32138

DO - 10.1002/ijc.32138

M3 - Article

AN - SCOPUS:85061234180

SN - 0020-7136

VL - 145

SP - 901

EP - 915

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 4

ER -