Lipid synthesis in mammalian cells
نویسندگان
چکیده
Cancer cells frequently exhibit specific alterations in their metabolic activity. This metabolic reprogramming supports the increased production of metabolic intermediates for the synthesis of proteins, nucleic acids and lipids, and is a prerequisite for the rapid proliferation of cancer cells. The most prominent metabolic alterations in cancer are an increase in glucose uptake and the use of aerobic glycolysis, termed the Warburg effect. However, other metabolic processes, including protein, nucleic acid and lipid biosynthesis, are also enhanced as part of cancer-associated metabolic reprogramming. The majority of adult mammalian tissues satisfy their lipid requirements through the uptake of free fatty acids (FFAs) and lipoproteins, such as low-density lipoprotein (LDL), from the bloodstream. Fatty acid (FA) and cholesterol biosynthesis are restricted to a subset of tissues, including liver, adipose and lactating breast tissues. However, reactivation of lipid biosynthesis is frequently observed in cancer tissue (reviewed by Menendez and Lupu, 2007). Over the past few years, increasing attention has been given to the study of the metabolic processes involved in lipid biosynthesis and their regulation within the context of this disease. In this Review, we will highlight some of the recent evidence implicating deregulated lipid biosynthesis in cancer development. We will focus on the contribution of some of the key enzymes involved in FA and cholesterol biosynthesis to cell transformation and cancer development. We will discuss their regulation by oncogenic signalling pathways and by the environmental conditions in growing tumours. Finally, we will examine how deregulated lipid metabolism in cancer cells might contribute to the complex interactions between cancer cells and the variety of stromal cell types that are recruited into the tumour. Because stromal cells play a vital role in cancer development and disease progression, targeting lipid metabolism in cancer cells could have therapeutic benefits.
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