DAB2IP Downregulation Enhances the Proliferation and Metastasis of Human Gastric Cancer Cells by Derepressing the ERK1/2 Pathway

Abstract

DAB2IP (DOC2/DAB2 interactive protein) is downregulated in several cancer types, and its downregulation is involved in tumor cell proliferation, apoptosis, metastasis, and epithelial-mesenchymal transition (EMT). We aimed to investigate the potential role of DAB2IP in the development and progression of gastric cancer. DAB2IP levels were analyzed in human gastric cancer and adjacent normal tissues by Western blots and immunohistochemistry. Potential roles of DAB2IP in regulating gastric cancer cell growth and metastasis were examined by genetic manipulation in vitro. The molecular signaling was determined to understand the mechanisms of observed DAB2IP effects. DAB2IP level is lower in gastric cancer tissues as compared to paired normal tissues. Knockdown of DAB2IP enhanced gastric cancer cell growth and metastasis in vitro and promoted EMT progress at both protein and mRNA levels. Silencing DAB2IP activated extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, and the enhanced proliferation and migration ability induced by DAB2IP knockdown were reduced after incubation with U0126 in SGC7901 gastric cancer cells. Inhibition of DAB2IP enhances gastric cancer cell growth and metastasis through targeting the ERK1/2 signaling, indicating that it may serve as a potential target for treatment of gastric cancer.