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.
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.
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.
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.
Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM.
Encouraging increases in the NSCLC response rate have already been reported after the addition of an anti-IGF-1R antibody to first-line carboplatin and paclitaxel.
These data show that IGF-I is overexpressed in NSCLC, leading to activation of IGF-IR, and that IGFBP-3, depending on its expression level, either inhibits or potentiates IGF-I actions in lung carcinogenesis.
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.
Our findings suggest that rs5742714 in IGF1 may be a genetic modifier for NSCLC prognosis in this Chinese population, especially among patients with surgical operation.
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.
One recent phase III trial of the IGF-1R inhibitor figitumumab in patients with non-small-cell lung cancer was discontinued after an interim analysis showed no survival improvement.
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.
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.