Is there any cross-talk between the Wnt and the Akt pathways?
['Our data demonstrate that engaging Wnt signaling at the receptor level by this method leads to necessary crosstalk between multiple signaling pathways including activation of Akt, mTOR, Wnt/β-catenin, PKA/CREB, and inhibition of RhoA/ROCK that substantially increase human β-cell proliferation while maintaining the β-cell phenotype.', 'The cross-talk role of Wnt/β-catenin and PI3K/Akt signaling pathway, with GSK-3β as the key enzyme bridging these pathways, may contribute to the inhibition of cholangiocarcinoma cells by hUC-MSCs.', 'We find that Wnt stimulation leads to phosphorylation of insulin signaling key mediators, including Akt, GSK3β, and ERK1/2, although with a lower fold stimulation and slower time course than observed for insulin.', 'Wnt induces phosphorylation of Akt, ERK1/2, and GSK3β, and this is dependent on insulin/IGF-1 receptors.', 'Pharmacologic inhibition of PI3K resulted in the downregulation of several members of the β-catenin pathway, including Fra-1, c-Myc, and cyclin D1.', 'Similar results were observed in vivo, as intratumoral injection of LY294002 downregulated the expression of the components of the β-catenin pathway and delayed tumor growth in nude mice harboring subcutaneous LN229 xenografts.', 'These results suggest that the PI3K/AKT signaling pathway regulates glioma cell proliferation, in part via repression of the Wnt/β-catenin pathway.', 'Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth', 'Small-molecule inhibitors targeting the PI3K/Akt signaling pathway affected beta-catenin signaling by activation [corrected] of GSK-3beta, [corrected] resulting in cytoplasmic retention of beta-catenin and reduced expression of its target genes cyclin D1 and c-Myc.', 'These findings demonstrate the importance of cross-talk between the PI3K/Akt and beta-catenin pathways in medulloblastoma and rationalize the PI3K/Akt signaling pathway as a therapeutic target in treatment of this disease.', 'Western blot analyses revealed that the recombinant Wnt ligand Wnt-3A increased phosphorylation of AKT and the downstream kinase glycogen synthase kinase (GSK)-3beta as well as accumulation of activated, nuclear beta-catenin.', 'Chemical inhibition of PI3K abolished Wnt-dependent phosphorylation of AKT and GSK-3beta and trophoblast motility but did not affect appearance of activated beta-catenin or Wnt/TCF reporter activity.', 'The data suggest that Wnt-3A may activate canonical Wnt signaling and PI3K/AKT through distinct receptors.', 'Mutational activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in a wide variety of tumors, whereas activating Wnt pathway mutants are predominantly found in colon cancer. Because GSK3 is a key component of both pathways, it is widely assumed that active PI3K signaling feeds positively into the Wnt pathway by protein kinase B (PKB)-mediatefd inhibition of GSK3.', 'n addition, PKB has been proposed to modulate the canonical Wnt signaling through direct stabilization and nuclear localization of beta-catenin.', 'Here, we show that compartmentalization by Axin of GSK3 prohibits cross-talk between the PI3K and Wnt pathways and that Wnt-mediated transcriptional activity is not modulated by activation of the PI3K/PKB pathway.', 'Our recent study revealed a second mechanism for Cby-mediated beta-catenin inhibition in which Cby cooperates with 14-3-3 adaptor proteins to facilitate nuclear export of beta-catenin, following phosphorylation of Cby by Akt kinase.', 'Therefore, our findings unravel a novel molecular mechanism regulating the dynamic nucleo-cytoplasmic trafficking of beta-catenin and provide new insights into the cross-talk between the Wnt and Akt signaling pathways.', 'Here, we review recent literature concerning Cby function and discuss our current understanding of the relationship between Wnt and Akt signaling.', 'As inappropriate activation of WNT/CTNNB1 signaling causes late-onset GCT development and cross talk between the PI3K/AKT and WNT/CTNNB1 pathways has been reported, we tested whether these pathways could synergize in GCT.', 'This explains why prostate tumors subjected to androgen ablation experience an increase in Akt phosphorylation, and suggest that the tumor compensates for the loss of one pathway with another. Different modes of interaction between the two pathways, including direct interaction, or regulation via downstream intermediates, such as the wnt/GSK-3beta/beta-catenin pathway, NF-kappaB, and the FOXO family of transcription factors, will be discussed.', 'FGF signals are transduced through FGF receptor to the FRS2-GRB2-GAB1-PI3K-AKT signaling cascade to downregulate GSK3beta activity depending on Ser 9 phosphorylation. Because GSK3beta-dependent phosphorylation of beta-catenin and SNAIL leads to FBXW1 (betaTRCP)-mediated ubiquitination and degradation, GSK3beta downregulation results in the stabilization and the nuclear accumulation of beta-catenin and SNAIL.', 'Bridging the BMP and Wnt pathways by PI3 kinase/Akt and 14-3-3zeta', 'Concurrently, PTEN, an inhibitor of PI3K/Akt pathway, is also primarily inactivated in the ISCs, leading to activation of Akt. Thus, Akt may contribute to activation of beta-catenin in ISCs in coordination with Wnt signaling.', 'Thus, we propose that BMP signaling plays a role in inhibition of ISC self-renewal through suppression of Wnt/beta-catenin signaling in ISC, and this cross-talk is bridged, at least in part, through the PTEN/Akt pathway and further enforced by 14-3-3zeta.', 'In MC3T3-E1 osteoblast-like cultures, dexamethasone (DEX) activates glycogen synthase kinase-3beta (GSK3beta) and inhibits a differentiation-related cell cycle that occurs at a commitment stage immediately after confluence.', 'Here we show that DEX inhibition of the differentiation-related cell cycle is associated with a decrease in beta-catenin levels and inhibition of LEF/TCF-mediated transcription.', 'These inhibitory activities are no longer observed in the presence of lithium, a GSK3beta inhibitor.', 'DEX decreased the serum-responsive phosphorylation of protein kinase B/Akt-Ser(473) within minutes, and this inhibition was also observed after 12 h. When the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was inhibited by wortmannin, DEX no longer inhibited beta-catenin levels.', 'Furthermore, DEX-mediated inhibition of LEF/TCF transcriptional activity was attenuated in the presence of dominant negative forms of either PI3K or protein kinase B/Akt. These results suggest cross-talk between the PI3K/Akt and Wnt signaling pathways.', 'These results suggest that inhibition of a PI3K/Akt/GSK3beta/beta-catenin/LEF axis and stimulation of HDAC1 cooperate to mediate the inhibitory effect of DEX on Wnt signaling and the osteoblast differentiation-related cell cycle.', 'WISP-1 (Wnt-1-induced secreted protein) was identified as an oncogene regulated by the Wnt-1-beta-catenin pathway.', 'Here it is shown that WISP-1 can activate the antiapoptotic Akt/PKB signaling pathway. ', 'Our results show that both TGFβ1 and Wnt3a lead to increased accumulation of β-catenin, phosphorylation of AKT and p44/42 MAPK.']
['The Wnt/β-catenin and PI3K/Akt signaling pathways cross-talk mainly through the activity of GSK-3β, a common component of both pathways, but also through the activity of other signaling transducers, such as Cby or WISP-1.']
['yes']