Signal transduction PTEN pathway
PTEN pathway Phosphatase and tensin homolog ( PTEN ) is a known tumor suppressor. Itinhibits growth factor-induced cell proliferation, division and regulates Integrin-mediated cell adhesion and survival . PTEN antagonizes Phosphoinositide-3-kinase ( PI3K ), dephosphorylatingPhosphatidylinositol (3,4,5) ( PtdIns(3,4,5)P3 ) and inhibits V-akt murine thymomaviral oncogene homolog 1 ( PI3K )/ AKT -mediated signaling pathways .As a result, PTEN prevents Insulin-like growth factor 1 ( IGF-1 )signaling ,  and activation of the Epidermal growthfactor receptor ( EGFR )-induced FK506 binding protein 12-rapamycin associatedprotein 1 ( mTOR ) . PTEN also inhibits Mdm2 p53 bindingprotein homolog ( MDM2 ) and protects Tumor protein p53 ( p53 ) viaPI3K/ AKT -dependent as well as via direct binding of p53 thusblocking antiapoptotic processes ,. Prevention ofPI3K/ AKT pathway activation by PTEN also increases activity ofGlycogen synthase kinase 3 ( GSK3 ). This leads to decrease of Beta-cateninnuclear accumulation and prevents transcription of the Transcription factor 7 (in acomplex Tcf(Lef) ) and others genes. Thus, PTEN antagonizesIntegrin/Integrin-linked kinase ( ILK )-mediated nuclear accumulation ofBeta-catenin . Inhibition of PI3K/ AKT decreasesCyclin-dependent kinase inhibitor 1A ( p21 )-mediated cell cycle regulation . PTEN -dependent PI3K/AKT inhibition also decreases Caspase 9apoptosis-related cysteine peptidase ( Caspase-9 ) activity , aswell as the apoptosis mediated by Forkhead box O3 ( FOXO3A )-mediated  and BCL2-associated agonist of cell death ( BAD ) . PTEN dephosphorylates PTK2 protein tyrosine kinase 2 ( FAK1 ) and SHCtransforming protein 1 ( Shc ). This prevents Integrin (for examplealpha-5/beta-1 integrin )/ FAK1 and Shc/ Growth factorreceptor-bound protein 2 ( GRB2 ) ,  and EGF/ Shc/ GRB2 -mediated  Mitogen-activated protein kinase 1/3( ERK1/2 ) activation. ERK1/2 inhibition prevents cell spreading, migration,  and growth. Dephosphorylation of FAK1 alsodisrupts its binding of Paxillin and Breast cancer anti-estrogen resistance 1 (p130CAS ) . PTEN binds Membrane associated guanylate kinase WW and PDZ domain containing (MAGI ) proteins. This enhances the efficiency of PTEN signaling through theformation of the PTEN/ MAGI complexes . Caspase 3apoptosis-related cysteine peptidase ( Caspase-3 ) cleaves PTEN. Thisinhibits the PTEN pathway .