In addition to selective inhibitors of ERK1/2, AKT, IKBα and NF-κβ, as therapeutic options, our data, for the first time, indicates carbonic anhydrase I and II as attractive targets for development of diagnostic tools enabling selection of patients for a more specific therapy in NSCLC.
Our data show that combined targeting of MEK and PI3K-AKT with mTOR is a better option than single agents alone for KRAS mutant NSCLC, thus opening the possibility of a beneficial treatment strategy in the future.
In this study, we showed that salinomycin (0.5-2μg/mL) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells.
Dual inhibition of the HSP90 and MEK signaling pathways with sub-therapeutic doses may represent a potent therapeutic strategy to treat KRAS-mutant NSCLC with intrinsic resistance to MEK inhibition and to resolve the toxicity observed upon dual inhibition of AKT and MEK at therapeutic doses in clinical trials.
Cells were immunomagnetically separated from samples of pleural effusion in patients with NSCLC. p-AKT, p-S6K and p-GSK3β levels were quantified by ELISA; targeted next-generation sequencing was used to characterise mutations in 26 genes.
In conclusion, LncRNA BC087858 could promote cells invasion and induce non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT via up- regulating ZEB1 and Snail in NSCLC.
A bioinformatics technique and western blot analyses showed that the PI3K/AKT pathway is more activated in EGFR-mutated NSCLC than in MET-amplified NSCLC, and a PI3K inhibitor enhanced the sensitivity to trametinib in the EGFR-mutated cell lines, suggesting that this pathway is associated with resistance to MEK inhibitors.
EZH2 overexpression induces murine lung cancers that are similar to human NSCLC with high EZH2 expression and low levels of phosphorylated AKT and ERK, implicating biomarkers for EZH2 inhibitor sensitivity.
Treatment of AKT inhibitor markedly prevented the phosphorylation of AKT and GSK3β which subsequently counteracted increasing expression of CyclinD1, CyclinE1 or Snail and restored the decreasing expression of Zo-1, as well as the upregulation of tumor proliferation and invasion, caused by ZNF452 overexpression.Taken together, the present study indicated that ZNF452 may be an upstream regulator of AKT-GSK3β signaling pathway and facilitates proliferation and invasion of NSCLC.
In this study, we showed that erlotinib (1.25-10μM) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung squamous cell carcinoma H1703 and adenocarcinoma H1975 cells.
Our data suggest that the combinations of inhibitors of AKT or autophagy together with glucose deprivation could be novel treatment strategies for NSCLC with acquired resistance to targeted therapy.
This study unravels an anti-metastatic role of AKT1 in the NSCLC cells with KRAS or EGFR mutations, and establishes an AKT1-MARCKS-LAMC2 feedback loop in this regulation.
In summary, our findings revealed a regulatory mechanism of NSCLC metastasis through EGFR-PI3K/AKT-FOXA1-PLOD2 pathway, and provided PLOD2 as a therapeutic target for NSCLC treatment.
Compared with adjacent normal tissue, the miR-205 and AKT gene expression level was significantly increased in NSCLC tissues (P<0.05) and the AKT protein expression was stronger than that of healthy tissues, miR-205 was positive correlation with AKT; In the overall survival, MiR-205 high expression group was significantly higher than low expression group (P<0.05).
FAL1 may promote tumorigenesis and progression of NSCLC through the PTEN/AKT axis, which could lead to lncRNA-related diagnostics and therapeutics in NSCLC.
In conclusion, Lasp1 facilitated tumor proliferation and invasion of NSCLC through directly binding to FAK and enhancing the phosphorylation of FAK (Tyr397) and AKT (Ser473).
In the present study, we investigated the effect of Akt1 on homologous recombination (HR)-dependent repair of radiation-induced DSBs in non-small cell lung cancer (NSCLC) cells A549 and H460.
To conclude, our study demonstrated that RAGE played a crucial role in the metastasis and growth of NSCLC by regulating PI3K/AKT and KRAS/RAF-1 signaling pathways, thereby might be a promising therapeutic target for NSCLC.