Dgkz-KO Mouse

Dgkz, or diacylglycerol kinase ζ, is a diacylglycerol kinase that metabolizes diacylglycerol to yield phosphatidic acid. It is involved in lipid signaling pathways, which are fundamental to neural activities, memory, and learning [3]. It also seems to be associated with several biological processes and disease-related pathways, such as the transforming growth factor β (TGFβ) signaling pathway [1].

In triple-negative breast cancer, knockout of Dgkz in cell lines significantly inhibited metastatic behaviors in vitro and in vivo, indicating its role as a prometastatic gene, possibly by promoting epithelial-mesenchymal transition via the TGFβ signaling pathway [1]. In osteosarcoma, silence of Dgkz by shRNA hampered cell growth and promoted apoptosis in vitro, and its knockout suppressed xenograft tumor proliferation in vivo. It might act as an oncogene through its possible interaction with ERK1/2 and MYC pathway [2]. In cervical cancer, down-regulation of Dgkz repressed cell proliferation, boosted apoptosis, and induced cell cycle arrest, and its knockdown restrained tumor growth in xenograft mice [4]. In human acute myeloid leukemia HL-60 cells, knockdown of Dgkz induced apoptosis and G2/M phase arrest through the MAPK/survivin/caspase pathway [5].

In conclusion, Dgkz is involved in multiple disease-related biological processes. Gene knockout and knockdown studies in various cell lines and in vivo models have revealed its role in promoting tumor metastasis, cell proliferation, and suppressing apoptosis in cancers such as triple-negative breast cancer, osteosarcoma, cervical cancer, and acute myeloid leukemia. These findings suggest Dgkz could be a potential target for cancer treatment and a prognostic indicator [1,2,4,5].

References:

1. Zhao, Yuanyuan, Sun, Hefen, Li, Xuan, Hou, Yifeng, Jin, Wei. 2022. DGKZ promotes TGFβ signaling pathway and metastasis in triple-negative breast cancer by suppressing lipid raft-dependent endocytosis of TGFβR2. In Cell death & disease, 13, 105. doi:10.1038/s41419-022-04537-x. https://pubmed.ncbi.nlm.nih.gov/35115500/

2. Yu, Wenxi, Tang, Lina, Lin, Feng, Yao, Yang, Shen, Zan. 2019. DGKZ Acts as a Potential Oncogene in Osteosarcoma Proliferation Through Its Possible Interaction With ERK1/2 and MYC Pathway. In Frontiers in oncology, 8, 655. doi:10.3389/fonc.2018.00655. https://pubmed.ncbi.nlm.nih.gov/30662872/

3. Alinaghi, Somayeh, Alehabib, Elham, Johari, Amir Hossein, Darvish, Hossein, Ghaedi, Hamid. 2019. Expression analysis and genotyping of DGKZ: a GWAS-derived risk gene for schizophrenia. In Molecular biology reports, 46, 4105-4111. doi:10.1007/s11033-019-04860-1. https://pubmed.ncbi.nlm.nih.gov/31087244/

4. Liu, Keying, Xue, Biyun, Bai, Guiqin, Zhang, Wentao. . Downregulation of Diacylglycerol kinase zeta (DGKZ) suppresses tumorigenesis and progression of cervical cancer by facilitating cell apoptosis and cell cycle arrest. In Bioengineered, 12, 1517-1529. doi:10.1080/21655979.2021.1918505. https://pubmed.ncbi.nlm.nih.gov/33926342/

5. Li, Hong, Dong, Changhu, Tian, Yanning, Bai, Yingying, Chao, Xu. . Knockdown of diacylglycerol kinase zeta (DGKZ) induces apoptosis and G2/M phase arrest in human acute myeloid leukemia HL-60 cells through MAPK/survivin/caspase pathway. In Die Pharmazie, 74, 418-422. doi:10.1691/ph.2019.9386. https://pubmed.ncbi.nlm.nih.gov/31288898/