LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer
| Autor: | Saša Frank, Kathrin Gianmoena, Carsten Watzl, Alshaimaa Adawy, Jan G. Hengstler, Katharina Grgas, Joanna Stewart, Cheng Cheng Zhang, Rosemarie Marchan, Fredrik Pontén, Birte Hellwig, Heiko Hayen, Alexander Schriewer, Cristina Cadenas, Dennis Franckenstein, Jörg Rahnenführer, Maren Claus, Michaela S. Lesjak, Patrick Micke, Sonja Vosbeck, Annika Glotzbach, Sonja Thaler, Karolina Edlund, Katrin Madjar, Adil Mardinoglu, Marcus Schmidt, Heiko U. Käfferlein |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Endothelial lipase
Cancer Research Medicin och hälsovetenskap lipid droplets LIPG Breast Neoplasms Oxidative phosphorylation oxidative stress breast cancer PLIN2 TXNRD1 endothelial lipase medicine.disease_cause Medical and Health Sciences Disease-Free Survival Metastasis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Lipid droplet medicine Humans Cancer och onkologi Clinical Laboratory Medicine Chemistry Cancer AMPK Lipase Middle Aged Lipid Metabolism medicine.disease Lipids Up-Regulation Klinisk laboratoriemedicin Oxidative Stress Oncology Cancer and Oncology 030220 oncology & carcinogenesis Disease Progression MCF-7 Cells Cancer research Female Lipoproteins HDL Cancer Epidemiology Oxidative stress |
| Zdroj: | International journal of cancer, 145(4):901-915 Cadenas, C, Vosbeck, S, Edlund, K, Grgas, K, Madjar, K, Hellwig, B, Adawy, A, Glotzbach, A, Stewart, J D, Lesjak, M S, Franckenstein, D, Claus, M, Hayen, H, Schriewer, A, Gianmoena, K, Thaler, S, Schmidt, M, Micke, P, Pontén, F, Mardinoglu, A, Zhang, C, Käfferlein, H U, Watzl, C, Frank, S, Rahnenführer, J, Marchan, R & Hengstler, J G 2019, ' LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer ', International Journal of Cancer, vol. 145, no. 4, pp. 901-915 . https://doi.org/10.1002/ijc.32138 International Journal of Cancer |
| DOI: | 10.1002/ijc.32138 |
| Popis: | 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. What's new? Endothelial lipase (LIPG), a cell surface‐associated lipase with multifaceted roles, is expressed on breast cancer cells, but its molecular function and clinical relevance remain unknown. Here the authors uncover a link between oxidative stress and LIPG upregulation and show that high LIPG expression is associated with shorter metastasis‐free survival in women with node‐negative breast cancer. The authors speculate that LIPG may favor metastasis by enabling stress adaptation through lipid droplet formation and protection of mitochondria. |
| Databáze: | OpenAIRE |
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