The transcription factor carbohydrate-response element-binding protein (ChREBP): A possible link between metabolic disease and cancer

Carbohydrate-response element-binding protein (ChREBP) has been identified as a transcription factor that binds to carbohydrate response element in the promoter of pyruvate kinase, liver and red blood cells. ChREBP is activated by metabolites derived from glucose and suppressed by adenosine monophosphate (AMP), ketone bodies and cyclic cAMP. ChREBP regulates gene transcription related to glucose and lipid metabolism. Findings from knockout mice and human subjects suggest that ChREBP helps to induce hepatic steatosis, dyslipidemia, and glucose intolerance. Moreover, in tumor cells, ChREBP promotes aerobic glycolysis through p53 inhibition, resulting in tumor cell proliferation. Anti-diabetic and anti-lipidemic drugs such as atorvastatin, metformin, bile acid sequestrants, docosahexaenoic acid and eicosapentaenoic acid may affect ChREBP transactivity. Secretory proteins such as fibroblast growth factor 21 and ANGPTL8 (Betatrophin) may be promising candidates for biologic markers reflecting ChREBP transactivity. Thus, ChREBP is associated with metabolic diseases and cancers, and may be a link between them.