High expression of DJ‐1 promotes growth and invasion via the PTEN‐AKT pathway and predicts a poor prognosis in colorectal cancer

摘要

Cancer cell invasion and unlimited proliferation are key factors in patients with colorectal cancer (CRC). Increased protein deglycase DJ‐1 in cancer cells is known to promote tumor growth; however, its role in CRC progression is not well defined. In this study, we investigated 100 CRC patients with disease stages I–IV to determine whether DJ‐1 could serve as a prognostic biomarker in CRC. These results showed that DJ‐1 expression in CRC tissues was higher than that in normal colon tissues and was associated with the (Tumor Node Metastasis) TNM stage. CRC patients with low DJ‐1 expression had a longer overall survival than those with high expression, and multivariate and univariate analyses indicated that DJ‐1 expression was an independent prognostic factor for overall survival in CRC. Furthermore, DJ‐1 overexpression in two colon cancer cell lines, HCT116 and style="fixed-case">SW480, activated protein kinase style="fixed-case">AKT and downregulated tumor suppressor style="fixed-case">PTEN, whereas style="fixed-case">DJ‐1 knockdown upregulated style="fixed-case">PTEN expression and effectively suppressed style="fixed-case">CRC cell invasion and proliferation both in vitro and in vivo, revealing a mechanism underlying style="fixed-case">DJ‐1 pro‐oncogenic activity in style="fixed-case">CRC. Treatment of style="fixed-case">MK2206, the specific style="fixed-case">AKT inhibitor, significantly decreased style="fixed-case">DJ‐1‐mediated cell proliferation and mobility in vitro. Taken together, these results suggest that style="fixed-case">DJ‐1 may be a novel prognostic biomarker and potential therapeutic target in human style="fixed-case">CRC.