Impact of <i>GFRA1</i> gene reactivation by DNA demethylation on prognosis of patients with metastatic colon cancer
Wanru Ma, Peng Xu, Zhaojun Liu, Jing Zhou, Liankun Gu, Jun Zhang, Dajun Deng
Abstract
BACKGROUND: CpG islands (dmGFRA1) is associated with increased gene expression and metastasis risk of gastric cancer. However, it is unknown whether dmGFRA1 affects the metastasis of other cancers, including colon cancer (CC). AIM: To study whether dmGFRA1 is a driver for CC metastasis and GFRA1 is a potential therapeutic target. METHODS: . The phosphorylation of AKT and ERK proteins was examined by Western blot analysis. RESULTS: overexpression markedly increased the phosphorylation levels of AKT and ERK proteins, two key molecules in two classic GFRA1 downstream pathways. CONCLUSION: expression is frequently reactivated by DNA demethylation in CC tissues and is significantly associated with a poor prognosis in patients with CC, especially those with metastatic CC. GFRA1 can promote the proliferation/growth of CC cells, probably by the activation of AKT and ERK pathways. GFRA1 might be a therapeutic target for CC patients, especially those with metastatic potential.