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LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 4, p. 901-915Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 145, no 4, p. 901-915
Keywords [en]
LIPG, PLIN2, TXNRD1, breast cancer, endothelial lipase, lipid droplets, oxidative stress
National Category
Clinical Laboratory Medicine Cancer and Oncology
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-380591DOI: 10.1002/ijc.32138ISI: 000472571300005PubMedID: 30653260OAI: oai:DiVA.org:uu-380591DiVA, id: diva2:1300635
Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2019-08-16Bibliographically approved

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