mTOR and AMP-Activated Protein Kinase in Obesity and Cancer

The mTOR (mechanistic target of rapamycin) is the main regulator of important cellular processes, including cellular growth, proliferation, protein synthesis, protein remodeling, autophagy, and cell metabolism in response to nutrition status, growth factor, and stress signals. Previous studies demonstrated that mTOR signaling plays a crucial role in the function of adipose tissue such as adipogenesis, lipid metabolism, thermogenesis, and adipokine biosynthesis and release. Nutritional status in adipose tissues is different than its surrounding microenvironment, which receive altered metabolic ques. from the adipose tissues. In regard to its critical role in cellular processes, it is expected that obesity and related metabolic disorders will have direct role in dysregulation of mTOR signaling. Aberrant mTOR signaling is commonly observed in different types of cancer. Hyperactivation of mTORC1 pathway activates cell proliferation and decreased autophagy, which leads to initiation of tumor growth, progression, and angiogenesis. Another regulator of metabolic activity, adenosine monophosphate (AMP)-activated protein kinase (AMPK), maintains the energy homeostasis in response to metabolic alteration. Previous research demonstrated that AMPK is a key cellular energy sensor responsible for regulating the metabolic activity of brown and beige adipose tissues. AMPK has also been demonstrated to negatively regulate diabetes, cardiovascular disease, and other metabolic syndromes. Apart from metabolic syndrome and diabetes, the AMPK signaling has shown therapeutic potential due to its unique potential in regulating of cancer cell proliferation via cell metabolism reprogramming.. Previous reports suggest the tumor suppressive role of AMPK that sense the energy deficiency in solid tumors, thereby inhibit the cellular proliferation. However, recent data proposes that tumor cells gain growth advantage in oxygen and nutrient deprived condition via exploiting AMPK activation. In light of adipose tissue associated tumors, it is well known that adipose tissues activate inflammation in response oxygen deprivation. However, the role of altered metabolism, specifically interaction between adipose tissues and tumor microenvironment, in terms of mTOR and AMPK signaling is not well known.