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

Abstract

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.

The Hepatic Microenvironment Uniquely Protects Leukemia Cells through Induction of Growth and Survival Pathways Mediated by LIPG

“…Upregulation of LIPG has been reported as a mechanism for accommodating elevated level of reactive oxygen species (ROS) (32). Enrichment of oxidative phosphorylation pathway ( Fig.2A) Research.…”

Highlight report: Role of PD-L1 in never-smokers

“…Predicting prognosis and response to therapy remains a challenging task (Hellwig et al, 2016[ 14 ]; Lohr et al, 2015[ 18 ]; Weisner et al, 2019[ 28 ]) with many modifying factors, e.g. proliferation (Siggelkow et al, 2012[ 26 ]), antioxidative status (Cadenas et al, 2010[ 4 ], 2014[ 5 ], 2019[ 6 ]) and metabolism (Marchan et al, 2017[ 19 ]; Stewart et al, 2012[ 27 ]) playing an important role. The present study of Edlund and colleagues helps to gain an overview which key factors modify the prognostic role of tumor infiltrating lymphocytes.…”

LIPG supports adaption to oxidative stress

“…Recently, Cadenas and colleagues reported that the endothelial lipase (LIPG) is upregulated during oxidative stress and supports survival of cells that are no longer able to generate a sufficient supply of fatty acids by de novo synthesis (Cadenas et al, 2019[ 3 ]). LIPG is a cell surface associated lipase that cleaves phosphatidylcholine from high-density lipoproteins (Jaye et al, 1999[ 10 ]; Choi et al, 2002[ 5 ]).…”

“…In the present study, Cadenas and colleagues used overexpression and knockdown strategies to demonstrate that LIPG enables breast cancer cell lines to utilize circulating lipoproteins to synthetize and store triglycerides in lipid droplets (Cadenas et al, 2019[ 3 ]). Moreover, the authors showed that oxidative stress under conditions that block endogenous fatty acid synthesis induces LIPG expression and activity.…”

“…Moreover, the authors showed that oxidative stress under conditions that block endogenous fatty acid synthesis induces LIPG expression and activity. Induction of LIPG was also observed after pharmacological inhibition of de novo fatty acid synthesis (Cadenas et al, 2019[ 3 ]). A key observation of the present study is that LIPG upregulation protects the cells from mitochondrial dysfunction and cell death.…”