Abstract
Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is a member of dual-specificity kinase family, which could phosphorylate both Ser/Thr and Tyr substrates. The role of DYRK2 in human cancer remains controversial. For example, overexpression of DYRK2 predicts a better survival in human non-small cell lung cancer. In contrast, amplification of DYRK2 gene occurs in esophageal/lung adenocarcinoma, implying the role of DYRK2 as a potential oncogene. However, its clinical role in colorectal cancer (CRC) has not been explored. In this study, we analyzed the expression of DYRK2 from Oncomine database and found that DYRK2 level is lower in primary or metastatic CRC compared to adjacent normal colon tissue or non-metastatic CRC, respectively, in 6 colorectal carcinoma data sets. The correlation between DYRK2 expression and clinical outcome in 181 CRC patients was also investigated by real-time PCR and IHC. DYRK2 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues. Functional studies confirmed that DYRK2 inhibited cell invasion and migration in both HCT116 and SW480 cells and functioned as a tumor suppressor in CRC cells. Furthermore, the lower DYRK2 levels were correlated with tumor sites (P = 0.023), advanced clinical stages (P = 0.006) and shorter survival in the advanced clinical stages. Univariate and multivariate analyses indicated that DYRK2 expression was an independent prognostic factor (P < 0.001). Taking all, we concluded that DYRK2 a novel prognostic biomarker of human colorectal cancer.
Highlights
Dual-specificity tyrosine-phosphorylation-regulated kinase, including dual-specificity yakrelated kinases (DYRKs) represent a large family of dual-specificity kinase, which can phosphorylate both Ser/Thr and Tyr substrates
In colorectal cancer (CRC), Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) level was found lower in primary or metastatic CRC compared with adjacent normal colon tissues or non-metastatic CRC in all 6 colorectal carcinoma data sets respectively
Pairs of normal rectum and primary rectal adenocarcinoma, the level of DYRK2 is lower in cancer tissue compared to paired adjacent normal tissues significantly (Fig 1A)
Summary
Dual-specificity tyrosine-phosphorylation-regulated kinase, including dual-specificity yakrelated kinases (DYRKs) represent a large family of dual-specificity kinase, which can phosphorylate both Ser/Thr and Tyr substrates. The DYRKs are evolutionarily conserved in their kinase domain, but differ from each other in the N- and C-terminal regions. These kinase domains have several distinct amino-acid sequences, including a DYRK homology (DH) box immediately preceding the kinase domain, a YXY motif in the kinase-domain-activation loop between subdomains VII and VIII, an SSC motif following sub domain VII, and conserved sequences HCDLKPEN and YXYIQSRFYR (S/A) PE in subdomains VI and VIII [2]. DYRK1A/1B and DYRK3 may serve as protective kinases against apoptosis [4,5,6] In specific tissues, such as neurons, muscle and blood cells, DYRK1A/1B and DYRK3 play a role during cell differentiation [7,8,9]. Down-regulation of DYRK2 could induce a G2/M arrest [11]
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