Fig. 1

Glucose metabolic reprogramming in obesity-associated endometrial cancer (EC). Obesity with increased visceral adipose tissue is a remarkable feature of EC and contributes to its tumorigenesis and progression through regulation of both systematic metabolism and cellular metabolism. Obesity leads to multiple risk factors of EC including excessive estrogen, abnormal lipid profile, dysregulated adipokines, insulin resistance and hyperglycaemia. Dyslipidemia exists in EC patients especially in those combined with hypothyroidism, including increased level of total cholesterol (TC), low triglycerides (TG), density lipoprotein (LDL)-cholesterol, and reduced level of high-density lipoprotein (HDL)-cholesterol. Dysregulated adipokines are closely associated with insulin resistance, which is primary pathophysiological basis of EC. Insulin directly or synergistically with estrogen promotes malignancy of EC cells through downstream PI3K/Akt and MEK/ERK signaling pathways. Visfatin has similar effects through activation of insulin receptor (InsR) and its substrate. Glucose enters into EC cells through glucose transporters (GLUT) and rewires cellular glucose metabolism. Increased expression or activity of glycolytic enzymes including hexokinase 2 (HK2), phosphoglucose isomerase (PGI), pyruvate kinase isozymes M2 (PKM2), lactate dehydrogenase (LDH) and mitochondrial enzyme malate dehydrogenase 2 (MDH2) in EC tissues may cause metabolic reprogramming which regulates EC cellular behavior