The emerging role of PPAR-alpha in breast cancer

Breast cancer has been confirmed to have lipid disorders in the tumour microenvironment. Peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcriptional factor that belongs to the family of nuclear receptors. PPARα regulates the expression of genes involved in fatty acid homeostasis and is a major regulator of lipid metabolism. Because of its effects on lipid metabolism, an increasing number of studies have investigated the relationship of PPARα with breast cancer. PPARα has been shown to impact the cell cycle and apoptosis in normal cells and tumoral cells through regulating genes of the lipogenic pathway, fatty acid oxidation, fatty acid activation, and uptake of exogenous fatty acids. Besides, PPARα is involved in the regulation of the tumour microenvironment (anti-inflammation and inhibition of angiogenesis) by modulating different signal pathways such as NF-κB and PI3K/AKT/mTOR. Some synthetic PPARα ligands are used in adjuvant therapy for breast cancer. PPARα agonists are reported to reduce the side effects of chemotherapy and endocrine therapy. In addition, PPARα agonists enhance the curative effects of targeted therapy and radiation therapy. Interestingly, with the emerging role of immunotherapy, attention has been focused on the tumour microenvironment. The dual functions of PPARα agonists in immunotherapy need further research. This review aims to consolidate the operations of PPARα in lipid-related and other ways, as well as discuss the current and potential applications of PPARα agonists in tackling breast cancer.