Dclk1, or Doublecortin-like kinase 1, is a microtubule-associated protein kinase. It is involved in neurogenesis and has been identified as a stem cell marker in various tissues. Dclk1 regulates tumorigenesis, epithelial-mesenchymal transformation, and is associated with multiple signaling pathways like Notch, Wnt/β-catenin, and RAS [3,5,6]. It also plays a role in maintaining epithelial homeostasis and the immune response [4].

In atherosclerosis, macrophage-specific Dclk1 deletion in ApoE-/-mice attenuates the disease by reducing inflammation. Mechanistically, Dclk1 binds to IKKβ, phosphorylates it at S177/181, and activates the NF-κB signaling pathway in macrophages, promoting inflammatory gene expression [1]. In obesity-induced cardiomyopathy, macrophage-specific Dclk1 knockout, but not cardiomyocyte-specific knockout, prevents HFD-induced heart dysfunction, hypertrophy, and fibrosis. Dclk1 deficiency suppresses RIP2/TAK1 activation and inflammatory responses in macrophages [2].

In conclusion, Dclk1 is crucial in multiple biological processes and disease conditions. Model-based research, especially using Dclk1 KO/CKO mouse models, has revealed its pro-inflammatory roles in atherosclerosis and obesity-induced cardiomyopathy, highlighting its potential as a therapeutic target for these inflammatory cardiovascular diseases [1,2].

References:

1. Huang, Zhuqi, Shen, Sirui, Han, Xue, Wu, Gaojun, Liang, Guang. 2023. Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses. In EMBO molecular medicine, 15, e17198. doi:10.15252/emmm.202217198. https://pubmed.ncbi.nlm.nih.gov/36896602/

2. Yang, Bin, Zhao, Yunjie, Luo, Wu, Wang, Yi, Liang, Guang. 2023. Macrophage DCLK1 promotes obesity-induced cardiomyopathy via activating RIP2/TAK1 signaling pathway. In Cell death & disease, 14, 419. doi:10.1038/s41419-023-05960-4. https://pubmed.ncbi.nlm.nih.gov/37443105/

3. Lu, Qin, Feng, Hailan, Chen, Hong, Yan, Zixing, Cao, Zhiyun. 2022. Role of DCLK1 in oncogenic signaling (Review). In International journal of oncology, 61, . doi:10.3892/ijo.2022.5427. https://pubmed.ncbi.nlm.nih.gov/36148883/

4. Ding, Ling, Weygant, Nathaniel, Ding, Chenhuan, Lai, Yi, Li, He. 2023. DCLK1 and tuft cells: Immune-related functions and implications for cancer immunotherapy. In Critical reviews in oncology/hematology, 191, 104118. doi:10.1016/j.critrevonc.2023.104118. https://pubmed.ncbi.nlm.nih.gov/37660932/

5. Ye, Liu, Liu, Beibei, Huang, Jingling, Xu, Yungen, Wang, Shuping. 2023. DCLK1 and its oncogenic functions: A promising therapeutic target for cancers. In Life sciences, 336, 122294. doi:10.1016/j.lfs.2023.122294. https://pubmed.ncbi.nlm.nih.gov/38007147/

6. Vijai, Muthu, Baba, Mursaleen, Ramalingam, Satish, Thiyagaraj, Anand. 2021. DCLK1 and its interaction partners: An effective therapeutic target for colorectal cancer. In Oncology letters, 22, 850. doi:10.3892/ol.2021.13111. https://pubmed.ncbi.nlm.nih.gov/34733368/