Recognition of the opposing role of NOTCH1 in lung cancer, downstream pathways, and interacting proteins in each context may help direct the development of rational NOTCH1 pathway-dependent targeted therapies for specific tumor subsets of NSCLC.
These data revealed that the induction of EMT and CSC properties were involved in the lung cancer risk of PM2.5 in vivo, and blocking-up Notch1 may negatively regulate EMT and CSC to suppress the invasion and migration in vitro, thereby putatively serving as a novel therapeutic target for PM2.5 induced lung cancer.
Here we explored the relationship of three SNPs (rs3124599, rs3124607 and rs3124594) in Notch1 with the risk and the survival of lung cancer in non-smoking females, including 556 cases and 395 controls.
Notably, treatment with a γ-secretase inhibitor that blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum sensitivity <i>in vitro</i> and <i>in vivo</i> Overall, our results define the pathogenic characters of a cancer stem-like subpopulation in lung cancer, the targeting of which may relieve platinum resistance in this disease.<i></i>.
The Notch1 siRNA can effectively inhibit the expression of Notch1 gene, inhibit the proliferation of lung cancer A549 cells and increase the sensitivity to chemotherapeutic drugs.
Finally, 34 lung cancer samples analyzed through direct sequencing indicated smoking significantly increased small nucleotide polymorphisms (SNPs) in Notch 1 and 2 and specific SNPs significantly modulated expression levels of downstream signaling pathway molecules.
It was recently reported that two receptors, Notch-1 and c-Met, correlate directly or indirectly with the initiation and development of malignant tumors, such as lung cancer; however, the prognostic value of coexpression of these receptors and their relationship in resected NSCLC was not clear.
Herein, we review recent findings about the role of NOTCH1 in lung cancer and discuss its potential usefulness as both a therapeutic target and a biomarker for lung cancer.
Silencing of Notch-1 using siRNA resulted in mesenchymal-epithelial transition (MET), which was associated with impaired invasion and anchorage-independent growth of lung cancer and resensitisation to gefitinib in acquired resistant NSCLC cells.
Potential ligand-binding sites within the epidermal growth factor (EGF)-like repeats of Notch1 have been identified, but the ligand-binding domains in Notch3, which is implicated in lung cancer, are not known.