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.

F.S., E.J.A. and G.T. are supported by the ‘La Caixa’ PhD Fellowship Program. FIS PI12/00680, PI12/01421 and PI12/01552 supported J.A., A.L. and F.R., respectively. J.A. is part of RD12/0036/0051, RD12/0036/0070 and RD12/0036/0042 and F.R. part of biobank PT13/0010/0012. J.A. is the recipient of ISCIII intensification Grant 2014SGR740, XBTC, MARBiobanc and Cellex. R.R.G. was supported by the Institució Catalana de Recerca i Estudis Avançats. Support and structural funds were provided by the BBVA Foundation, the Generalitat de Catalunya (2014 SGR 535) and the Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds (SAF2013-46196) to R.R.G. and (SAF2014-54525-P) to J.J.G.