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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