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

Slebe F, Rojo F, Vinaixa M, GarcĂ­a-Rocha M, Testoni G, Guiu M, Planet E, Samino S, Arenas EJ, Beltran A, Rovira A, Lluch A, Salvatella X, Yanes O, Albanell J, Guinovart JJ, Gomis RR
Source: Nat Commun.
Publication Date: (2016)
Issue: 7: 11199
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Epithelial, mammary, human (HMEC)
Species: human
Tissue Origin: breast
The researchers investigated the FoxA1 and LIPG lipid metabolic pathways in cancer mammary cells. they found that FoxA1 and transcription factors family regulate LIPG (lipoprotein lipase). Loss of LIPG activity impairs tumor growth. Lonza\\\'s HMECs were used as a control for normal cells.
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.