Inhibition of LIPG phospholipase activity suppresses tumor formation of human basal-like triple-negative breast cancer
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AbstractThe endothelial lipase LIPG possesses serine phospholipase activity and is involved in lipoprotein metabolism. Our previous studies have revealed that LIPG overexpression is required for tumor formation and metastasis of human basal-like triple-negative breast cancer (TNBC). We also demonstrated that LIPG differentially regulates TNBC malignancy through its enzymatic and non-enzymatic functions. The present studies were aimed at determining how XEN445, a specific inhibitor targeting LIPG phospholipase activity, impacts on TNBC tumor formation and malignant features. We established a cell-based LIPG enzymatic assay system to measure the inhibitory effect of XEN445 on LIPG phospholipase activity and determine its IC50. We found that XEN445 preferentially inhibited the proliferation of LIPG-expressing TNBC cells but not LIPG-negative luminal breast cancer cells. XEN445 inhibited the self-renewal of cancer stem cells (CSCs) in vitro and TNBC tumor formation in vivo. However, XEN445 had no inhibitory effect on the invasiveness and CSC stemness of TNBC cells. Our studies suggest that targeting both LIPG enzymatic and non-enzymatic functions is an important strategy for the treatment of TNBC. Copyright 2020, The Author(s).
SponsorsThis work was supported in part by Merit Review Award #1I01BX004264 from the United States (U.S.) Department of Veterans Affairs (Biomedical Laboratory Research and Development Service). This work was also supported by the NIH/NCI (R01CA157779).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85085710465&doi=10.1038%2fs41598-020-65400-7&partnerID=40&md5=895f0a2692a25393eeba622978b926dd; http://hdl.handle.net/10713/12974