Reversible phosphorylation is a fundamental mechanism to control all cell signaling and communication and this process is regulated through the opposing actions of phosphatases and kinases. Altered cellular signaling as a result of protein hyperphosphorylation, results in sustained proliferative signaling, and is a hallmark of human cancer development.
Protein Phosphatase 2A (PP2A) is a serine/threonine phosphatase that functions as a tumor suppressor by negatively regulating multiple oncogenic signaling pathways responsible for driving cancer progression. PP2A is made up of three subunits, that form a complete and active enzyme when bound together. The active enzyme is comprised of a scaffolding subunit (A), serving as the structural platform for the assembly of the catalytic (C) subunit and one substrate directing regulatory (B) subunit. In cancer, the tumor suppressive activity of PP2A is often disrupted as a result of the inability of the three subunits to bind together correctly, rendering the PP2A enzyme inactive. This inactivation of PP2A, leads to increased oncogenic signaling, driving cancer progression and growth. Therefore, the reactivation of PP2A affords a unique therapeutic strategy to restore PP2A activity and cellular homeostasis, that can potentially be used for the treatment of cancer and a broad range of other diseases.