PI3K/AKT pathway

PI3K/AKT pathway is a critical signaling pathway that influences various cellular processes including metabolism, growth, cell survival, and proliferation. This pathway is highly conserved across different species and plays a pivotal role in the development and progression of many diseases, particularly cancer.

Overview

The PI3K/AKT pathway is activated by various types of cellular stimuli or toxic insults, which leads to the activation of phosphoinositide 3-kinases (PI3K). PI3K then catalyzes the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the cell membrane. PIP3 serves as a secondary messenger that recruits and activates AKT (Protein Kinase B), among other proteins. Once activated, AKT phosphorylates a range of substrates involved in the regulation of cell survival, cell cycle progression, and cellular growth.

Key Components

• PI3K - A family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival, and intracellular trafficking, which in turn are involved in cancer progression.
• PTEN - A major negative regulator of the PI3K/AKT pathway. PTEN dephosphorylates PIP3, thus inhibiting AKT activation.
• AKT (Protein Kinase B) - A serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration.
• Mechanistic target of rapamycin (mTOR) - A downstream target of AKT. mTOR is a central regulator of cell growth and proliferation, linking AKT signaling to the control of protein synthesis and autophagy.

Regulation and Function

The PI3K/AKT pathway is tightly regulated by various mechanisms to prevent abnormal cell growth and proliferation. Dysregulation of this pathway has been implicated in numerous conditions, including cancer, cardiovascular diseases, and diabetes. In cancer, mutations in the PI3K pathway often lead to increased AKT activity, which can promote tumor growth and survival. Therapeutic strategies targeting the PI3K/AKT/mTOR pathway are being actively developed and include the use of small molecule inhibitors, monoclonal antibodies, and antisense oligonucleotides.

Clinical Implications

Due to its central role in cell survival and growth, the PI3K/AKT pathway is a primary target for cancer therapy. Inhibitors targeting PI3K, AKT, or mTOR are currently under clinical development and have shown promise in treating various types of cancer. Understanding the specific mutations and alterations in the PI3K/AKT pathway in different cancers can help in the design of targeted therapies that improve treatment outcomes.

See Also

• Cell signaling
• Oncogene
• Signal transduction