Akt1-flox Mouse

Akt1, also known as protein kinase B (PKB), is a serine/threonine kinase that plays a central role in cell survival pathways. It is a key transducer in the phosphoinositide-3-kinase (PI3K)/AKT pathway, which regulates cell survival and is over-activated in many human cancers. Akt1's activity is often studied through genetic models, which can help reveal its functions in various biological processes and disease conditions.

In cancer research, Akt1 has been found to have multiple impacts. It phosphorylates cytoplasmic malic enzyme 2 (ME2fl) at serine 9, preventing its mitochondrial translocation. This leads to a metabolic switch from mitochondrial metabolism to glycolysis, enhancing the glycolytic capacity of tumor cells in vitro and in vivo [1]. In lung cancer, abnormal activation of Akt1/2 is associated with osimertinib resistance, and costunolide, a dual inhibitor of MEK1 and Akt1/2, can overcome this resistance [2]. In triple-negative breast cancer, Akt1 phosphorylates FDX1, promoting cuproptosis resistance by inhibiting FDX1-induced cuproptosis and aerobic respiration while promoting glycolysis [3]. In pancreatic cancer, DUSP2 can suppress Akt1-mediated apoptosis resistance under hypoxic microenvironment by competing with Akt1 to bind to CSNK2A1 and inhibiting Akt1 phosphorylation [4].

In conclusion, Akt1 is crucial for cell survival and is deeply involved in the metabolic adaptation and survival mechanisms of tumor cells in various cancers. The study of Akt1 using genetic models has provided important insights into the molecular mechanisms of cancer development, which may potentially lead to the development of new therapeutic strategies targeting this key kinase.