Genetic alterations driving aberrant activation of the survival kinase Protein Kinase B (Akt) are observed with high frequency during malignant transformation and cancer progression.
The cytoplasmic domain is critical for that activation and involves focal adhesion kinase (FAK), extracellular regulated kinase (ERK1/2), and protein kinase B (AKT/PKB) signaling, further contributing to cancer progression and mediating chemoresistance against first-line therapies.
Since AKT and Stat3 play an important role in EMT and tumor progression, we examined whether there is a correlation between NFIB and AKT/Stat3 signaling pathways in GC.
Further, genome-wide gene expression analysis in EphA6 knock-down cells identified a panel of differentially regulated genes including PIK3IPA, AKT1, and EIF5A2, which could contribute to EphA6-regulated cancer progression.
Thus, our findings identify phospho-AKT in the primary tumor and miR-200c later during tumor progression as prognostic molecules and potential therapeutic targets to prevent progression and metastasis of pediatric osteosarcomas.
However, it has been found that AKT1 and AKT3 isoforms have a main role in tumor progression and metastasis; thus, the identification of AKT isoforms specific inhibitors seems to be a challenge.
The aim of the present study was to evaluate the impact of the expression of RANK and its downstream signaling molecule Akt1 on tumor progression in patients with osteosarcoma.
We showed that CXCL8 secreted by tumor cells at the invasion front were able to promote migration through angiogenesis by upregulating VEGFA and invasion via the AKT/GSK3β/β-catenin/MMP7 pathway by upregulating BCL-2 confirming the key role of CXCL8 during tumor progression.
TIS21<sup>/BTG2</sup> significantly lost in the infiltrating ductal carcinoma, but it can inhibit cancer growth via the TIS21<sup>/BTG2</sup>-tsc1/2-mTORc1-p70S6K axis and downregulate cancer progression via the TIS21<sup>/BTG2</sup>-mTORc2-AKT1-NFAT1-PHLPP2 pathway.
Mechanistically, high levels of TRIM44 increased the levels of p-AKT (T308) and p-mTOR (S2448), and a specific AKT inhibitor inhibited TRIM44-induced tumor progression.
We have previously demonstrated an increased expression of gastrin-releasing peptide (GRP) and its receptor, GRPR, in neuroblastoma and that GRP activates the PI3K-AKT pathway as a proangiogenic factor during tumor progression.
Endostar, a novel safe and well-tolerated recombinant human endostatin, can suppress the expression of VEGF and the activation of ERK, MAPK, and AKT, and then inhibit tumor progression.
Cytogenetic studies and mouse models are beginning to identify genes and signalling pathways that have roles in tumour progression, such as hedgehog, p53, insulin-like growth factor, cyclin-dependent kinase 4, hypoxia-inducible factor, matrix metalloproteinases, SRC and AKT, suggesting potential new therapeutic approaches.