DYRK2, short for dual-specificity tyrosine phosphorylation-regulated kinase 2, is a Ser/Thr kinase belonging to the CMGC kinase family. It plays crucial roles in regulating the cell cycle, apoptosis, DNA repair, and proteostasis [1-3, 5-8]. It is involved in multiple signaling pathways, such as phosphorylating p53 at Ser46 to induce apoptosis in response to DNA damage, and regulating Hedgehog signaling by phosphorylating GLI2/GLI3 [1,3,5]. Understanding DYRK2 is essential for uncovering the mechanisms of cell differentiation, tissue homeostasis, and diseases like cancer [1]. Genetic models, especially gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying DYRK2.

In colorectal cancer, DYRK2 knockout decreased chemosensitivity to 5-fluorouracil and oxaliplatin in p53 wild-type cells and xenograft mouse models, indicating its role in promoting chemosensitivity via p53-mediated apoptosis [3]. In chronic myeloid leukemia, DYRK2 controls the activation of p53 and proteasomal degradation of c-MYC, impairing the survival and self-renewal of leukemia stem cells, suggesting pharmacological activation of DYRK2 could potentially induce treatment-free remission [2]. In another study, DYRK2 downregulation in colorectal cancer led to epithelial-mesenchymal transition induction and chemoresistance, and overexpression of DYRK2 inhibited tumor growth in xenograft models [4].

In conclusion, DYRK2 is a key regulator in multiple biological processes. Model-based research, especially KO/CKO mouse models, has revealed its significance in cancer, including its roles in chemosensitivity, tumor cell survival, and epithelial-mesenchymal transition. These findings provide potential therapeutic targets for treating cancers like colorectal and chronic myeloid leukemia.