The Intersection of Anoikis Resistance and Fatty Acid Metabolism in Cancer

Anoikis resistance is an essential adaption of cancer cells to metastasize effectively. Normally, the detachment of epithelial cells from the extracellular matrix induces cellular stressors, including nutrient-deprivation and oxidative stress, and this elevated cellular stress leads to apoptosis. In contrast, cancer cells often have an increased capacity to adapt to cellular stressors, and these adaptations include metabolic reprogramming to account for the changing nutrient microenvironment. Thus, metabolic plasticity and anoikis resistance cooperate to promote disease progression. For instance, high grade serous ovarian carcinoma, when disseminating with the peritoneal cavity, must resist anoikis to colonize distant sites, and these sites are often fat-rich environments. Consistently, a whole genome-wide screen in ovarian cancer cells uncovered and reinforced the hypothesis that cancer cells enhance fatty acid oxidation activity to avoid anoikis and successfully colonize a secondary site. Targeting metabolic reprogramming and fatty acid oxidation is a feasible approach to inhibit cancer progression. Emphasizing ovarian cancer as a model system, this chapter will focus on the metabolic pathway, fatty acid oxidation, as a means of overcoming nutrient-deprivation induced stress to promote anoikis resistance. Further, the chapter will focus on the pathways involved in fatty acid oxidation regulation and strategies to attenuate metabolic plasticity and promote anoikis.