DYRK2 is a suppressor and potential prognostic marker for liver metastasis of colorectal cancer

Summary

Colorectal cancer is a common cancer and a leading cause of cancer-related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial-mesenchymal-transition (EMT) is the key step for metastasis of cancer cells. We have recently demonstrated in breast cancer and ovarian serous adenocarcinoma that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls EMT. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We demonstrated that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by an ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer.

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