Figure 5.

Schematic model of AREG in the Warburg effect and tumorigenesis. The influx of glucose is mainly mediated by GLUT1, a transporter molecule. The expression of GLUT1 was shown to be partly controlled by the AREG-EGFR pathway. The MLX transcription factor, which possibly forms a complex with MondoA, directly binds to the promoter region of AREG via ChoRE, resulting in enhanced AREG expression. AREG may transactivate EGFR and subsequently activate HIF-1, resulting in the induction of many genes associated with the Warburg effect. The MLX-MondoA complex likely promotes the expression of many genes associated with the Warburg effect, independent of HIF-1. The Warburg effect regulated by AREG may be involved in CRC tumorigenesis. AREG, amphiregulin; GLUT1, glucose transporter member 1; HIF, hypoxia-inducible factor; ChoRE, carbohydrate response element; CRC, colorectal cancer; EGFR, epidermal growth factor receptor; MLX, Max-like protein X.