Lipid Rafts as Master Regulators of Breast Cancer Cell Function
Cancer is a leading cause of death in developed countries, and is on the rise in developing countries due in part to a lack of prophylactic screening and non-universal access to medical care (Jemal et al., 2011). Breast cancer is initiated when breast epithelial cells escape growth arrest and form a proliferating tumour mass. Numerous cellular mechanisms are dysregulated in breast tumour cells, including modified cell fate, altered protein signalling and trafficking, and enhanced cell migratory potential. Although these events are complex and subject to regulation by multiple elements, recent evidence has suggested that specialised cell membrane domains termed lipid rafts are actively involved in each of these processes (Cary & Cooper, 2000; Nabi & Le, 2003; Simons & Toomre, 2000). This chapter will therefore focus on the contribution of lipid rafts to breast cancer initiation and progression under these headings.
Lipid rafts are sub-domains of the cell membrane enriched in cholesterol and glycosphingolipids (Le Moyec et al., 1992; Nohara et al., 1998). These microdomains cluster together proteins involved in the regulation of crucial cellular processes; many of which are altered in cancer cells (Pike, 2003; de Laurentiis et al., 2007). Furthermore, lipid rafts are readily modified by diet and nutrition (Schley et al., 2007; Yaqoob, 2009), and studies have shown that fatty acid supplementation sensitises human mammary tumour cells to the cytotoxic effects of anti-cancer agents in vitro and in vivo (Germain et al., 1998; Menendez et al., 2005; Colas et al., 2006). This chapter will focus on the potential regulatory functions of lipid rafts as a novel approach towards understanding mechanisms of cancer initiation, progression and cell migration, a key event preceding metastatic progression. Finally it will discuss the potential of lipid rafts as novel therapeutic targets in breast cancer.