<b>Conclusion:</b> ODC1 is an unfavorable gene in HCC patients,promoting HCC cell proliferation, migration and invasion via the AKT/GSK3β/β-catenin pathway and modulation of the acidotic microenvironment.
<b>Results:</b> Our data involving both gain- and loss-of-function studies revealed that VASP activated AKT and ERK signaling and promoted HCC migration and invasion in vitro and in vivo by altering the EMT phenotype and expression of MMPs.
Invasion responses were positively correlated with phosphorylation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and p42/p44 mitogen-activated protein kinase (ERK).
AKT kinases regulate diverse cellular processes including cell proliferation and survival, cell size and response to nutrient availability, tissue invasion and angiogenesis.
AKT mediates signal relay by phosphorylating numerous substrates, which are causally implicated in biologic responses such as cell growth, survival, metabolic reprogramming, migration, and invasion.
Akt1 deficient PCa cells exhibited enhanced cell migration and invasion in vitro and lung metastasis in vivo, which were attenuated by treatment with Nodal pathway inhibitor SB505124.
A few years ago, studies from several laboratories added a new layer to the pleiotropic effects of Akt function by showing that the Akt1 isoform inhibits breast cancer cell migration and invasion, whereas Akt2 promotes these phenotypes.
A Transwell assay and western blot analysis revealed that metformin inhibited the migration and invasion of EC109 cells, nuclear factor-κB activation, matrix metallopeptidase 9 and N-cadherin expression in a phosphorylated-AKT dependent manner.
Additionally, <i>in silico</i> analysis of TCGA database showed that AKT1 overexpression was present in 14.7% (41/279) of HNSCC cases, and was associated with perineural invasion in advanced stage.
Additionally, HIF-1α promoted the tumor cells growth, migration and invasion in osteosarcoma through the activation of the AKT/Cyclin D1 signal cascade.
Additionally, PTEN knockdown promoted the migration and invasion of cells and caused an obvious increase in p-AKT, p-GSK-3β, β-catenin, E-cadherin, MMP-7, MMP-2, and MMP-9 in gastric cancer cells.
After overexpressing miR-208, p-AKT and p-GSK-3β expression was altered by activating AKT/GSK-3β/snail signaling pathway. miR-208 induces epithelial to mesenchymal transition of pancreatic cancer cell line BxPC3 by activating AKT/GSK-3β/snail signaling pathway and thereby promotes cell metastasis and invasion.
All these results suggested that TRPV4 accelerates glioma migration and invasion through the AKT/Rac1 signaling, and TRPV4 might be considered as a potential target for glioma therapy.
Altogether, upregulation of RAGE expression is associated with lymph node metastases of gastric cancer, and blockade of RAGE signaling suppresses growth and invasion of gastric cancer cells through AKT pathway, suggesting that RAGE may represent a potential therapeutic target for this aggressive malignancy.
An increase in phosphorylated-AKT expression due to targeting of insulin-like growth factor-binding protein-3 by microRNA-125b was responsible for cell invasion in p53-mutated cells.
Antitumor effects of helenalin in doxorubicin-resistant leukemia cells are mediated via mitochondrial mediated apoptosis, loss of mitochondrial membrane potential, inhibition of cell migration and invasion and downregulation of PI3-kinase/AKT/m-TOR signalling pathway.