WTX beyond WNT signaling pathway

Abstract

Gastric cancer (GC) is a major malignancy in many developing countries with low early detection rate. As a tumour suppressor gene, WTX inhibits PI3K/AKT/mTOR pathway activity by inhibiting PI3K phosphorylation. WTX loss of WTX protein associates with tumor metastasis and poor survival of GC patients. During GC progression, an aberrantly elevated miR-20a-5p expression has been found, which inhibits WTX expression and induces PI3K phosphorylation, thereby activating the PI3K/AKT/mTOR pathway and promoting cellular proliferation and migration. A new mechanism in which miR-20a-5p promotes GC progression by regulating WTX expression to control PI3K/AKT/mTOR pathway activity has been recently discovered. These findings might be useful for developing novel therapeutics to inhibit the progression of GC.