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

Abstract

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 SW480, activated protein kinase AKT and downregulated tumor suppressor PTEN, whereas DJ-1 knockdown upregulated PTEN expression and effectively suppressed CRC cell invasion and proliferation both in vitro and in vivo, revealing a mechanism underlying DJ-1 pro-oncogenic activity in CRC. Treatment of MK2206, the specific AKT inhibitor, significantly decreased DJ-1-mediated cell proliferation and mobility in vitro. Taken together, these results suggest that DJ-1 may be a novel prognostic biomarker and potential therapeutic target in human CRC.

Our data suggest that DJ-1 may be a novel prognostic biomarker and a potential therapeutic target in human CRC.

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