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LIPG signaling promotes tumor initiation and metastasis of human basal-like triple-negative breast cancer.

eLife | 2018

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.

Pubmed ID: 29350614 RIS Download

Research resources used in this publication

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA157779
  • Agency: NCI NIH HHS, United States
    Id: R01 CA163820
  • Agency: NCI NIH HHS, United States
    Id: CA157779A1
  • Agency: NCI NIH HHS, United States
    Id: CA163820A1

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


BioLegend (tool)

RRID:SCR_001134

Commercial antibody supplier and developer for biomedical research. These products are compatible with use in flow cytometry and mass cytometry, immunoprecipitation and chip, western blotting, immunofluorescence microscopy, and quantitative multiplexing.

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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Jackson Laboratory (tool)

RRID:SCR_004633

An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.

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Ambion Inc. (tool)

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A division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.

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Interferome (tool)

RRID:SCR_007743

Interferome is a database that provides identification of interferon regulated gene signatures from high-throughput data sets (i.e. microarray, proteomic data etc.). It will also assist in identifying regulatory elements and enable comparison of tissue expression of IRGs in human and mouse. Availability of sequence information from more than 37 species, together with comprehensive annotation will enable comparative genomics and phylogenetic analysis to be performed on these IRGs. Within the database, Type I, II and III IFN regulated genes have been manually curated from more than 28 publicly available microarray datasets. Interferon Regulated Genes (IRGs) were identified from multiple microarray and proteomic experiments where cells were treated with IFNs. Genes that were up or down regulated more than 1.5 fold relative to control samples were defined as IRGs.

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UniProt (tool)

RRID:SCR_002380

Collection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.

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Cell Signaling Technology (tool)

RRID:SCR_004431

Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.

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Proteintech Group (tool)

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Crl:NU(NCr)-Foxn1nu (tool)

RRID:IMSR_CRL:490

Mus musculus with name Crl:NU(NCr)-Foxn1nu from IMSR.

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alpha Tubulin Monoclonal Antibody (TU-01) (antibody)

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This monoclonal targets alpha Tubulin

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PE anti-human CD24 (antibody)

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Vimentin antibody (antibody)

RRID:AB_2273020

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Vimentin Antibody (V9) (antibody)

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E-cadherin Monoclonal Antibody (6F9) (antibody)

RRID:AB_1955688

This monoclonal targets E-cadherin

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DTX3L/BBAP Antibody (antibody)

RRID:AB_2277461

This unknown targets DTX3L/BBAP

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ISG15 Antibody (antibody)

RRID:AB_2126201

This polyclonal targets ISG15

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LIPG antibody (antibody)

RRID:AB_943999

This monoclonal targets LIPG

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APC anti-mouse/human CD44 (antibody)

RRID:AB_312963

This monoclonal targets CD44

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MDA-MB-468 (cell line)

RRID:CVCL_0419

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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MCF-7 (cell line)

RRID:CVCL_0031

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Hs 578T (cell line)

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HEK293T (cell line)

RRID:CVCL_0063

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MDA-MB-231 (cell line)

RRID:CVCL_0062

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MCF10DCIS.com (cell line)

RRID:CVCL_5552

Cell line MCF10DCIS.com is a Transformed cell line with a species of origin Homo sapiens (Human)

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T-47D (cell line)

RRID:CVCL_0553

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Oncomine Research Platform (service resource)

RRID:SCR_007834

Oncomine Research Platform is a partially-commercial suite of products for online cancer gene expression analysis dedicated to the academic and non-profit research community. Oncomine combines a rapidly growing compendium of 20,000+ cancer transcriptome profiles with a sophisticated analysis engine and a powerful web application for data-mining and visualization. Oncomine facilitates rapid and reliable biomarker and therapeutic target discovery, validation and prioritization. Oncomine was developed by physicians, scientists, and software engineers at the University of Michigan and is now fully supported for the academic and non-profit research community by Compendia Bioscience.

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DTX3L/BBAP Antibody (antibody)

RRID:AB_2277461

This unknown targets DTX3L/BBAP

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ISG15 Antibody (antibody)

RRID:AB_2126201

This polyclonal targets ISG15

View all literature mentions

MCF-7 (cell line)

RRID:CVCL_0031

Cell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-468 (cell line)

RRID:CVCL_0419

Cell line MDA-MB-468 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Hs 578T (cell line)

RRID:CVCL_0332

Cell line Hs 578T is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Hs 578T (cell line)

RRID:CVCL_0332

Cell line Hs 578T is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Vimentin Antibody (V9) (antibody)

RRID:AB_2537032

This monoclonal targets Vimentin

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

E-cadherin Monoclonal Antibody (6F9) (antibody)

RRID:AB_1955688

This monoclonal targets E-cadherin

View all literature mentions

PE anti-human CD24 (antibody)

RRID:AB_314854

This monoclonal targets CD24

View all literature mentions

APC anti-mouse/human CD44 (antibody)

RRID:AB_312963

This monoclonal targets CD44

View all literature mentions

HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

alpha Tubulin Monoclonal Antibody (TU-01) (antibody)

RRID:AB_2533035

This monoclonal targets alpha Tubulin

View all literature mentions

DTX3L/BBAP Antibody (antibody)

RRID:AB_2277461

This unknown targets DTX3L/BBAP

View all literature mentions

LIPG antibody (antibody)

RRID:AB_943999

This monoclonal targets LIPG

View all literature mentions

LIPG antibody (antibody)

RRID:AB_943999

This monoclonal targets LIPG

View all literature mentions

Vimentin antibody (antibody)

RRID:AB_2273020

This polyclonal targets Vimentin

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

MCF10DCIS.com (cell line)

RRID:CVCL_5552

Cell line MCF10DCIS.com is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Vimentin Antibody (V9) (antibody)

RRID:AB_2537032

This monoclonal targets Vimentin

View all literature mentions

E-cadherin Monoclonal Antibody (6F9) (antibody)

RRID:AB_1955688

This monoclonal targets E-cadherin

View all literature mentions

T-47D (cell line)

RRID:CVCL_0553

Cell line T-47D is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

APC anti-mouse/human CD44 (antibody)

RRID:AB_312963

This monoclonal targets CD44

View all literature mentions

PE anti-human CD24 (antibody)

RRID:AB_314854

This monoclonal targets CD24

View all literature mentions

alpha Tubulin Monoclonal Antibody (TU-01) (antibody)

RRID:AB_2533035

This monoclonal targets alpha Tubulin

View all literature mentions

MDA-MB-231 (cell line)

RRID:CVCL_0062

Cell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

ISG15 Antibody (antibody)

RRID:AB_2126201

This polyclonal targets ISG15

View all literature mentions

Vimentin antibody (antibody)

RRID:AB_2273020

This polyclonal targets Vimentin

View all literature mentions

DTX3L/BBAP Antibody (antibody)

RRID:AB_2277461

This unknown targets DTX3L/BBAP

View all literature mentions

MCF10DCIS.com (cell line)

RRID:CVCL_5552

Cell line MCF10DCIS.com is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

LIPG antibody (antibody)

RRID:AB_943999

This monoclonal targets LIPG

View all literature mentions

HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

T-47D (cell line)

RRID:CVCL_0553

Cell line T-47D is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MCF-7 (cell line)

RRID:CVCL_0031

Cell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-468 (cell line)

RRID:CVCL_0419

Cell line MDA-MB-468 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-231 (cell line)

RRID:CVCL_0062

Cell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Hs 578T (cell line)

RRID:CVCL_0332

Cell line Hs 578T is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions