Lipid biology of breast cancer

Abstract

Alterations in lipid metabolism have been reported in many types of cancer. Lipids have been implicated in the regulation of proliferation, differentiation, apoptosis, inflammation, autophagy, motility and membrane homeostasis. It is required that their biosynthesis is tightly regulated to ensure homeostasis and to prevent unnecessary energy expenditure. This review focuses on the emerging understanding of the role of lipids and lipogenic pathway regulation in breast cancer, including parallels drawn from the study of metabolic disease models, and suggestions on how these findings can potentially be exploited to promote gains in HER2/neu-positive breast cancer research. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.

Keywords: Breast cancer; HER2/neu; Metabolism; Signaling.

Figure 1. Integrated model of lipogenic tumor biology in HER2/neu-positive breast cancer

Recurrent genomic amplification of chromosome 17q12-21 results in a prolipogenic signal transduction and transcriptional program. The resulting upregulation of HER2 and the transcription factors NR1D1 and PBP positively influences the production and/or function of lipogenic transcription factors SREBP and PPARγ. The concomitant activation of the unfolded protein response has the potential to further manifest and strengthen a lipogenic metabolic phenotype that is uniquely capable of sustaining cell growth, proliferation, migratory capacity and chemoresistance. This altered lipid metabolism phenotype is likely to affect tumor progression and metastasis in vivo.