{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["7"],"submitter":["Lo PK"],"funding":["NCI NIH HHS"],"pubmed_abstract":["Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC. Mechanistically, LIPG executes its oncogenic function through its involvement in interferon-related DTX3L-ISG15 signaling, which regulates protein function and stability by ISGylation. We show that DTX3L, an E3-ubiquitin ligase, is required for maintaining LIPG protein levels in TNBC cells by inhibiting proteasome-mediated LIPG degradation. Inactivation of LIPG impairs DTX3L-ISG15 signaling, indicating the existence of DTX3L-LIPG-ISG15 signaling. We further reveal LIPG-ISG15 signaling is lipase-independent. We demonstrate that DTX3L-LIPG-ISG15 signaling is essential for malignancies of TNBC cells. Targeting this pathway provides a novel strategy for basal-like TNBC therapy."],"journal":["eLife"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5809145"],"repository":["biostudies-literature"],"pubmed_title":["LIPG signaling promotes tumor initiation and metastasis of human basal-like triple-negative breast cancer."],"pmcid":["PMC5809145"],"funding_grant_id":["CA163820A1","R01 CA163820","R01 CA157779","CA157779A1"],"pubmed_authors":["Lee JS","Kane MA","Yao Y","Zhou Q","Zhang Y","Huang W","Lo PK"],"additional_accession":[]},"is_claimable":false,"name":"LIPG signaling promotes tumor initiation and metastasis of human basal-like triple-negative breast cancer.","description":"Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC. Mechanistically, LIPG executes its oncogenic function through its involvement in interferon-related DTX3L-ISG15 signaling, which regulates protein function and stability by ISGylation. We show that DTX3L, an E3-ubiquitin ligase, is required for maintaining LIPG protein levels in TNBC cells by inhibiting proteasome-mediated LIPG degradation. Inactivation of LIPG impairs DTX3L-ISG15 signaling, indicating the existence of DTX3L-LIPG-ISG15 signaling. We further reveal LIPG-ISG15 signaling is lipase-independent. We demonstrate that DTX3L-LIPG-ISG15 signaling is essential for malignancies of TNBC cells. Targeting this pathway provides a novel strategy for basal-like TNBC therapy.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Jan","modification":"2021-02-19T09:14:47Z","creation":"2019-03-26T23:02:57Z"},"accession":"S-EPMC5809145","cross_references":{"pubmed":["29350614"],"doi":["10.7554/eLife.31334"]}}