title: FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth.
abstract: The mechanisms that allow breast cancer (BCa) cells to metabolically sustain rapid growth are poorly understood. Here we report that BCa cells are dependent on a mechanism to supply precursors for intracellular lipid production derived from extracellular sources and that the endothelial lipase (LIPG) fulfils this function. LIPG expression allows the import of lipid precursors, thereby contributing to BCa proliferation. LIPG stands out as an essential component of the lipid metabolic adaptations that BCa cells, and not normal tissue, must undergo to support high proliferation rates. LIPG is ubiquitously and highly expressed under the control of FoxA1 or FoxA2 in all BCa subtypes. The downregulation of either LIPG or FoxA in transformed cells results in decreased proliferation and impaired synthesis of intracellular lipids.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Slebe
authors.affiliation: Cancer Research Programme, IMIM (Hospital del Mar Medical Research Institute), Barcelona 08003 Spain.|Pathology Department, IIS-Fundación Jimenez Diaz, Madrid 28040, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.affiliation: Centre for Omic Sciences, Universitat Rovira i Virgili, Reus 43204, Spain.|Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona 43003, Spain.|Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid 28029, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vinaixa
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: García-Rocha
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Testoni
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Guiu
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
authors.forename: Evarist
authors.initials: E
authors.lastname: Planet
authors.affiliation: Centre for Omic Sciences, Universitat Rovira i Virgili, Reus 43204, Spain.|Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid 28029, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Samino
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Arenas
authors.affiliation: Centre for Omic Sciences, Universitat Rovira i Virgili, Reus 43204, Spain.|Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid 28029, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Beltran
authors.affiliation: Cancer Research Programme, IMIM (Hospital del Mar Medical Research Institute), Barcelona 08003 Spain.|Medical Oncology Service, Hospital del Mar, Barcelona 08003, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rovira
authors.affiliation: Medical Oncology Service, Hospital Clinico, Valencia 46010, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Salvatella
authors.affiliation: Centre for Omic Sciences, Universitat Rovira i Virgili, Reus 43204, Spain.|Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona 43003, Spain.|Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid 28029, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Yanes
authors.affiliation: Cancer Research Programme, IMIM (Hospital del Mar Medical Research Institute), Barcelona 08003 Spain.|Medical Oncology Service, Hospital del Mar, Barcelona 08003, Spain.|Universitat Pompeu Fabra, Barcelona 08003, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.|Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid 28029, Spain.|Department of Biochemistry and Molecular Biology, Universitat de Barcelona, Barcelona 08028, Spain.
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Guinovart
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.
authors.forename: Roger R
authors.initials: RR
authors.lastname: Gomis
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051542:Hepatocyte Nuclear Factor 3-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics*; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D000077403:Orlistat; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; D004791:Enzyme Inhibitors; C496499:FOXA1 protein, human; C496502:FOXA2 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D007783:Lactones; D034741:RNA, Small Interfering; D051542:Hepatocyte Nuclear Factor 3-beta; D000077403:Orlistat; C410382:LIPG protein, human; D008049:Lipase; D004318:Doxycycline; D015107:4-Butyrolactone