Akt1-KO Mouse

Akt1, also known as protein kinase B, is a serine/threonine kinase and a central transducer of cell survival pathways. It is involved in multiple key biological processes such as cell growth, metabolism, and apoptosis, and is a crucial component of the phosphoinositide-3-kinase (PI3K)/AKT pathway, which is over-activated in most human cancers [4,6].

In cancer research, activation of AKT1 can induce a metabolic switch to glycolysis from mitochondrial metabolism via phosphorylating cytoplasmic malic enzyme 2 (ME2), promoting tumorigenesis [1]. In triple-negative breast cancer, AKT1 phosphorylates FDX1 to promote cuproptosis resistance [5]. In lung cancer, inhibition of AKT1/2 can overcome osimertinib resistance [2]. In pancreatic cancer, DUSP2 can suppress AKT1-mediated apoptosis resistance under hypoxic microenvironment [7]. In breast cancer cells, changes in AKT1 levels lead to alterations in the expression of a set of genes [3]. In ovarian cancer, miRNAs can regulate AKT1 phosphorylation [4].

In conclusion, Akt1 plays essential roles in various biological processes and disease conditions, especially in cancer. Studies using different models have revealed its complex functions in tumor metabolism, drug resistance, apoptosis, and gene expression regulation, providing valuable insights for understanding disease mechanisms and developing potential therapeutic strategies.

References:

1. Chen, Taiqi, Xie, Siyi, Cheng, Jie, Jiang, Peng, Du, Wenjing. 2024. AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis. In Nature communications, 15, 686. doi:10.1038/s41467-024-44772-8. https://pubmed.ncbi.nlm.nih.gov/38263319/

2. Tian, Xueli, Wang, Rui, Gu, Tingxuan, Lee, Mee-Hyun, Dong, Zigang. 2022. Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer. In Molecular cancer, 21, 193. doi:10.1186/s12943-022-01662-1. https://pubmed.ncbi.nlm.nih.gov/36203195/

3. George, Bijesh, Gui, Bin, Raguraman, Rajeswari, Pillai, Madhavan Radhakrishna, Kumar, Rakesh. 2022. AKT1 Transcriptomic Landscape in Breast Cancer Cells. In Cells, 11, . doi:10.3390/cells11152290. https://pubmed.ncbi.nlm.nih.gov/35892586/

4. Frederick, Mallory I, Siddika, Tarana, Zhang, Pengcheng, O'Donoghue, Patrick, Heinemann, Ilka U. 2022. miRNA-Dependent Regulation of AKT1 Phosphorylation. In Cells, 11, . doi:10.3390/cells11050821. https://pubmed.ncbi.nlm.nih.gov/35269443/

5. Sun, Zicheng, Xu, Huazhen, Lu, Guanming, Guo, Jianping, Li, Jie. 2025. AKT1 Phosphorylates FDX1 to Promote Cuproptosis Resistance in Triple-Negative Breast Cancer. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2408106. doi:10.1002/advs.202408106. https://pubmed.ncbi.nlm.nih.gov/39976173/

6. Siddika, Tarana, Balasuriya, Nileeka, Frederick, Mallory I, Heinemann, Ilka U, O'Donoghue, Patrick. 2022. Delivery of Active AKT1 to Human Cells. In Cells, 11, . doi:10.3390/cells11233834. https://pubmed.ncbi.nlm.nih.gov/36497091/

7. Zhang, Yangyang, Kong, Rui, Yang, Wenbo, Hu, Jisheng, Sun, Bei. 2023. DUSP2 recruits CSNK2A1 to suppress AKT1-mediated apoptosis resistance under hypoxic microenvironment in pancreatic cancer. In Cancer letters, 568, 216288. doi:10.1016/j.canlet.2023.216288. https://pubmed.ncbi.nlm.nih.gov/37390887/