PI3-kinase p110α mediates β1 integrin-induced Akt activation and membrane protrusion during cell attachment and initial spreading

Characterization of Heparanase-induced Phosphatidylinositol 3-Kinase-AKT Activation and Its Integrin Dependence

“…(iii) The activation of PI3K/AKT by heparanase was inefficient if the PI3K-RAS interaction was prevented (Fig. 3C) as shown previously for ␤1 integrin ligands, EGF and FGF2, whereas the interaction was dispensable for PDGF stimulation of AKT (19,33). (iv) Integrin-mediated adhesion strongly promoted the heparanase response (Fig.…”

“…For example, whereas the EGF receptor and ␤1 integrins utilize the p110␣ isoform (19,33), G protein-coupled lysophosphatidic acid receptors prefer the p110␤ catalytic subunit (34). Because the receptor(s) that mediates heparanase signaling is not known, identification of the PI3K catalytic subunit(s) involved in heparanase-mediated AKT activation may help in identifying this elusive receptor(s).…”

“…1-3) and integrin-induced activation of the PI3K-AKT pathway (24,33,35) and the ability of heparanase to activate integrins (16,36), we examined whether increased AKT phosphorylation by heparanase involved integrins. Addition of heparanase to adherent MCF7 cells resulted in ϳ5-fold increased AKT phosphorylation (Fig.…”

Common and Diverging Integrin Signals Downstream of Adhesion and Mechanical Stimuli and Their Interplay with Reactive Oxygen Species

“…This was the case also for the reactions driving integrin-dependent actin polymerization. The polymerization was monitored as lamellipodia protrusion from the initial contact points of attaching cells by live cell total internal reflection fluorescence (TIRF) microscopy, and this assay could detect the response to integrin ligand binding as early as after a few seconds (5,9). Possibly, the contribution of myosin-dependent contractile force becomes important at later time points or affects other signaling reactions.…”

“…Invasive growth and metastasis require cell migration, which depends on membrane protrusions at the cell front driven by actin polymerization and detachment at the rear driven by actin-myosin contraction. Both reactions are potently induced by integrins (2,9). The invasive phenotype in carcinomas is linked to TGFβ-induced epithelial-mesenchymal transition, and the activation of the latent TGFβ complex occurs mainly via binding to integrin αvβ6 in carcinomas (10).…”