Our data demonstrate that SphK1 acts as a downstream effector of IGF-1 and plays a critical role in IGF-1-induced EMT, cell migration and paclitaxel resistance of A549 cells, suggesting that SphK1 might be a potential therapeutic target for NSCLC.
Together, these results reveal that the stress hormone NE accelerates Afatinib resistance by increasing the expression of Cx32, which augments MET and IGF-1R levels in cancer cells and provides a promising therapeutic strategy against EGFR-TKI Afatinib resistance in NSCLC.
Additionally, GSEA found that LINC01614 might be involved in TGF-β-, P53-, IGF-IR-mediated, Wnt and RTK/Ras/MAPK signaling pathways.lncRNAs may play key roles in the development of NSCLC.
Taken together, these findings indicate that CAFs promote EGFR-TKIs resistance through HGF/IGF-1/ANXA2/EMT signaling and may be an ideal therapeutic target in NSCLCs with EGFR-activating mutations.
ADAM28 (a disintegrin and metalloproteinase 28) is overexpressed by carcinoma cells in non-small cell lung carcinomas (NSCLC) and plays an important role in cancer cell proliferation and metastasis by reactivation of insulin-like growth factor-1 (IGF-1) and escaping from von Willebrand factor (VWF)-induced apoptosis through digestion of IGF-binding protein-3 and VWF, respectively.
The high expression of GP130 and IGF-1R is an independent risk factor for poor prognosis patients, and it is helpful to find a more accurate target for targeted therapy in NSCLC.
Then, IGF-dependent signaling was assessed after expressing wild-type or a mutant IGFBP3 without IGF binding capacity in non-small cell lung cancer (NSCLC) cells.
Taken together, these results suggest a potential role for EI24 as a biomarker of drug resistance, and indicate that combination therapy with EGFR and IGF-1R inhibitors would be effective in NSCLC patients with low EI24 expression.
We found that glucosamine inhibited the growth of human non-small cell lung cancer (NSCLC) cells and negatively regulated the expression of IGF-1R and phosphorylation of Akt.
IGF-1R acts as a predictor for resistance to gefitinib in NSCLC cell lines and NSCLC patients, but does not seem to play a role in the intrinsic resistance to this drug.