FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth

Felipe Slebe; Federico Rojo; Maria Vinaixa; Mar García-Rocha; Giorgia Testoni; Marc Guiu; Evarist Planet; Sara Samino; Enrique J Arenas; Antoni Beltran; Ana Rovira; Ana Lluch; Xavier Salvatella; Oscar Yanes; Joan Albanell; Joan J Guinovart; Roger R Gomis

doi:10.1038/ncomms11199

FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth

Nat Commun. 2016 Apr 5:7:11199. doi: 10.1038/ncomms11199.

Authors

Felipe Slebe¹, Federico Rojo^{2

3}, Maria Vinaixa^{4

5

6}, Mar García-Rocha¹, Giorgia Testoni¹, Marc Guiu¹, Evarist Planet¹, Sara Samino^{4

6}, Enrique J Arenas¹, Antoni Beltran^{4

6}, Ana Rovira^{2

7}, Ana Lluch⁸, Xavier Salvatella^{1

9}, Oscar Yanes^{4

5

6}, Joan Albanell^{2

7

10}, Joan J Guinovart^{1

6

11}, Roger R Gomis^{1

9}

Affiliations

¹ Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
² Cancer Research Programme, IMIM (Hospital del Mar Medical Research Institute), Barcelona 08003 Spain.
³ Pathology Department, IIS-Fundación Jimenez Diaz, Madrid 28040, Spain.
⁴ Centre for Omic Sciences, Universitat Rovira i Virgili, Reus 43204, Spain.
⁵ Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona 43003, Spain.
⁶ Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid 28029, Spain.
⁷ Medical Oncology Service, Hospital del Mar, Barcelona 08003, Spain.
⁸ Medical Oncology Service, Hospital Clinico, Valencia 46010, Spain.
⁹ Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.
¹⁰ Universitat Pompeu Fabra, Barcelona 08003, Spain.
¹¹ Department of Biochemistry and Molecular Biology, Universitat de Barcelona, Barcelona 08028, Spain.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

4-Butyrolactone / analogs & derivatives
4-Butyrolactone / pharmacology
Animals
Biological Transport
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Doxycycline / pharmacology
Enzyme Inhibitors / pharmacology
Female
Gene Expression Regulation, Neoplastic*
Hepatocyte Nuclear Factor 3-alpha / antagonists & inhibitors
Hepatocyte Nuclear Factor 3-alpha / genetics
Hepatocyte Nuclear Factor 3-alpha / metabolism*
Hepatocyte Nuclear Factor 3-beta / antagonists & inhibitors
Hepatocyte Nuclear Factor 3-beta / genetics
Hepatocyte Nuclear Factor 3-beta / metabolism*
Humans
Lactones / pharmacology
Lipase / antagonists & inhibitors
Lipase / genetics
Lipase / metabolism*
Lipid Metabolism / genetics*
MCF-7 Cells
Mice
Mice, Nude
Neoplasm Invasiveness
Orlistat
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Signal Transduction
Xenograft Model Antitumor Assays

Substances

4-methylene-2-octyl-5-oxofuran-3-carboxylic acid
Enzyme Inhibitors
FOXA1 protein, human
FOXA2 protein, human
Hepatocyte Nuclear Factor 3-alpha
Lactones
RNA, Small Interfering
Hepatocyte Nuclear Factor 3-beta
Orlistat
LIPG protein, human
Lipase
Doxycycline
4-Butyrolactone