Prkd3-KO Mouse

Prkd3, encoding protein kinase D3, is a serine/threonine protein kinase belonging to the protein kinase D family [3]. It is activated by stimuli like phorbol esters and G-protein-coupled receptor agonists. PRKD3 is involved in numerous cellular processes, and its dysregulation is associated with various diseases [3]. Genetic models, such as knockout mouse models, can be valuable for studying its function.

In cancer, PRKD3 promotes cell proliferation, growth, migration, and invasion in multiple tumor types including oral squamous cell carcinoma (OSCC), hepatocellular carcinoma (HCC), gastric cancer, and breast cancer. For example, in OSCC, high PRKD3 expression is related to distant metastasis and poor prognosis, and it may accelerate malignant progression by down-regulating KLF16 expression [1]. In HCC, knocking down PRKD3 inhibits cell proliferation, induces G2/M phase arrest, and affects proteins related to amino acid transport, stress response, and apoptosis [2]. In gastric cancer, PRKD3 knockdown impairs cell malignancy, leading to decreased proliferation, migration, and invasion, along with G2/M phase arrest and changes in proteins associated with tumor-related signaling pathways like FoxO and p53 [4]. In breast cancer, network analysis of PRKD3-regulated phosphoproteins, interacting proteins, and genes reveals its role in regulating pathways related to cell cycle and migration [5]. In addition, in mice, deletion of Prkd3 promotes liver fibrosis, as it skews macrophage polarization toward a profibrotic phenotype and affects phosphatase activity and signal transduction in macrophages [6].

In conclusion, Prkd3 plays a crucial role in cancer progression and liver fibrosis. Model-based research, especially knockout mouse models, has revealed its oncogenic role in promoting tumorigenesis in various cancers and its function in regulating liver fibrosis. Understanding Prkd3 provides insights into the mechanisms of these diseases and may offer potential therapeutic targets [1,2,4,5,6].

References:

1. Chen, Z, Huang, Q, Xu, W, Yang, J, Zhang, L-J. . PRKD3 promotes malignant progression of OSCC by downregulating KLF16 expression. In European review for medical and pharmacological sciences, 24, 12709-12716. doi:10.26355/eurrev_202012_24169. https://pubmed.ncbi.nlm.nih.gov/33378018/

2. Tian, Ye, Xie, Bei, Wang, Shuaiyang, Ma, Lei, Li, Linjing. 2024. PRKD3 promotes proliferation of liver cancer cells: a downstream proteomics profiling study. In American journal of translational research, 16, 6384-6398. doi:10.62347/YLJE5332. https://pubmed.ncbi.nlm.nih.gov/39678603/

3. Liu, Yan, Song, Hang, Zhou, Yehui, Yu, Zhenghong, Chen, Liming. 2021. The oncogenic role of protein kinase D3 in cancer. In Journal of Cancer, 12, 735-739. doi:10.7150/jca.50899. https://pubmed.ncbi.nlm.nih.gov/33403031/

4. Wang, Shuaiyang, Xie, Bei, Deng, Haohua, Li, Jing, Li, Linjing. 2025. Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks. In Medical oncology (Northwood, London, England), 42, 135. doi:10.1007/s12032-025-02663-y. https://pubmed.ncbi.nlm.nih.gov/40131654/

5. Liu, Yan, Li, Jian, Zhang, Jun, Gu, Jun, Chen, Liming. 2017. Oncogenic Protein Kinase D3 Regulating Networks in Invasive Breast Cancer. In International journal of biological sciences, 13, 748-758. doi:10.7150/ijbs.18472. https://pubmed.ncbi.nlm.nih.gov/28656000/

6. Zhang, Shuya, Liu, Huan, Yin, Meimei, Yamasaki, Sho, Jin, Zheng Gen. 2020. Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice. In Hepatology (Baltimore, Md.), 72, 1717-1734. doi:10.1002/hep.31176. https://pubmed.ncbi.nlm.nih.gov/32048304/