Fig. 1. PTEN exhibits tumor suppressive functions in the cytoplasm and nucleus.
The phosphatidylinositol 3-kinase (PI3K) pathway regulates cancer cell growth and survival. This pathway is activated by ligand binding to receptor tyrosine kinases (RTKs) and/or G protein coupled receptors (GPCRs). PI3K is then recruited to the membrane where it phosphorylates phosphatidylinositol (4,5)-bisphosphate (PIP2) to produce phosphatidylinositol (3,4,5)-trisphosphate (PIP3), leading to activation of several signaling cascades including AKT/mTORC1. Cytoplasmic PTEN negatively regulates this pathway by dephosphorylating PIP3 at its D3 position. Nuclear PTEN promotes chromosome stability and regulates DNA double-strand break repair. Red star indicates a potential therapeutic target for which a drug(s) is in development.
