AMPK, a key regulator of metabolic/energy homeostasis and mitochondrial biogenesis in cancer cells

Normal cellular physiology requires sufficient supply of nutrients for the generation of ATP, building blocks and reducing capacity. In contrast, rapid proliferation of tumor cells demands increased requirement of the fundamental building blocks, which in turn necessitates augmented utilization of nutrients as a carbon source. 1 However, owing to poor vasculature, availability of carbon and nitrogen sources and molecular oxygen is compromised, which leads to metabolic stress in solid tumors. 2 Under such conditions, intrinsically altered cancer cell metabolism generates heterogeneity in the concentrations of glucose and other metabolites, as well as oxygen and pH across the tumor. 2 Therefore, metabolic adaptation to altered and insufficient availability of nutrients and oxygen is critical for overall tumor progression. These conditions persuade a series of changes in the molecular or biochemical pathways, mediating the cellular stress responses under extreme conditions in tumor microenvironment, which are poorly understood.