Prkd3, also known as Protein kinase D 3, is a serine/threonine protein kinase belonging to the protein kinase D family. It is activated by stimuli like phorbol esters and G-protein-coupled receptor agonists. PRKD3 participates in multiple cellular processes such as cell proliferation, growth, migration, and invasion, playing a crucial role in various biological functions and disease-related pathways [3].

In cancer research, PRKD3 has been shown to promote the malignant progression of oral squamous cell carcinoma (OSCC), as its high expression in OSCC specimens is associated with distant metastasis and poor prognosis. Knocking down PRKD3 attenuates OSCC cells' migration and invasiveness [1]. In hepatocellular carcinoma (HCC), PRKD3 knockdown inhibits cell proliferation, inducing cell cycle arrest at G2/M phase. Proteomic analysis reveals proteins related to amino acid transport, stress response, and apoptosis are affected [2]. In gastric cancer, PRKD3 overexpression is linked to aggressive behaviors, and its knockdown impairs cell malignancy with G2/M phase arrest and alterations in key cell cycle proteins [4]. In invasive breast cancer, network analysis of PRKD3-regulated phosphoproteins, interacting proteins, and genes reveals hub nodes and enrichment in cancer-related pathways like cell cycle and migration [5]. In liver fibrosis, deletion of Prkd3 in mice (both global Prkd3 knockout and myeloid-cell-specific Prkd3 knockout) promotes liver fibrosis by skewing macrophage polarization towards a profibrotic phenotype [6].

In conclusion, Prkd3 is a significant regulator in multiple biological processes, especially in cancer and liver fibrosis. Studies using gene knockout mouse models have revealed its promoting role in cancer cell progression and its inhibitory role in liver fibrosis development. These findings provide potential therapeutic targets for treating related diseases.

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/