Vav3-KO Mouse

Vav3, a member of the VAV guanine nucleotide exchange factor family, is a versatile protein that functions as an adaptor mediator and GEF for Rho GTPase. It acts as a phosphorylation-dependent molecular switch, toggling between active (tyrosine phosphorylated) and inactive (non-phosphorylated) states in cell signaling. Vav3 is involved in various cellular processes and associated with multiple pathways, playing an important role in normal biological functions and disease development [1].

In cancer, studies have shown that VAV3 promotes cell proliferation, epithelial-mesenchymal transition (EMT), colony formation, cell cycle progression, survival, migration, and invasion, while suppressing apoptosis, suggesting an oncogenic role [1]. In glioblastoma, knockdown of VAV3 using shRNA significantly inhibited cell migration, invasion, and proliferation, as well as stem-like cell self-renewal, indicating it could be a potential biomarker and therapeutic target [3]. In B-cell lymphoblastic leukemia, nuclear Vav3 is required for polycomb repression complex-1 activity in leukemogenesis, and its deficiency leads to de-repression of negative regulators of cell proliferation and repression of oncogenic transcriptional factors [4]. In metabolic-associated fatty liver disease (MAFLD), activation of STAT3 induced by a high-fat diet suppresses the expression of VAV3, and VAV3 deficiency impairs glucose homeostasis and cholesterol metabolism. Restoration of VAV3 expression in mice improved glucose homeostasis and attenuated hepatic cholesterol accumulation [2].

In conclusion, Vav3 has diverse functions in different biological processes and diseases. Genetic models such as knockdown or knockout in cancer, leukemia, and MAFLD studies have revealed its role in promoting cancer progression, leukemogenesis, and influencing glucolipid metabolism. Understanding Vav3's functions through these model-based research provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Al-Hawary, Sulieman Ibraheem Shelash, Alsalamy, Ali, Gupta, Reena, Ahmed, Muhja, Hosseini-Fard, Seyed Reza. 2023. VAV3 in human cancers: Mechanism and clinical implication. In Pathology, research and practice, 248, 154681. doi:10.1016/j.prp.2023.154681. https://pubmed.ncbi.nlm.nih.gov/37467637/

2. Jiang, Yue, Luo, Pengcheng, Cao, Yu, Lin, Li, Lv, Jiagao. 2024. The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD. In International journal of biological sciences, 20, 2027-2043. doi:10.7150/ijbs.86465. https://pubmed.ncbi.nlm.nih.gov/38617550/

3. Miao, Rui, Huang, Dong, Zhao, Kaitao, Cheng, Yi, Guo, Na. 2023. VAV3 regulates glioblastoma cell proliferation, migration, invasion and cancer stem‑like cell self‑renewal. In Molecular medicine reports, 27, . doi:10.3892/mmr.2023.12981. https://pubmed.ncbi.nlm.nih.gov/36960857/

4. Nayak, R C, Chang, K H, Singh, A K, Nassar, N N, Cancelas, J A. 2022. Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis. In Nature communications, 13, 3056. doi:10.1038/s41467-022-30651-7. https://pubmed.ncbi.nlm.nih.gov/35650206/