In conclusion, the c.599C>G mutation may be a new single nucleotide polymorphism of IL6ST, but mutations in exon 6 of this gene are not apparently common genetic variations occurring and leading to constitutive activation of STAT3 in lung cancer.
STAT3rs4769793 G allele carriers had an increased susceptibility of lung cancer [additive model: adjusted OR (95% CI) 1.376 (1.058-1.789), P = 0.017; recessive model: adjusted OR (95% CI) 1.734 (1.007-2.985), P = 0.047].
STAT3 CC (rs3 816 769) and AA genotypes (rs744 166) were associated with lower lung cancer risk, whereas TT (rs3 816 769) and GG genotypes (rs744 166) were found to be associated with significantly elevated lung cancer risk.
We initially analyzed expression and phosphorylation of ERBB family receptors and their major downstream proteins, AKT, p44/42 MAPK and STAT3, in a series of lung cancer cell lines with or without EGFR mutation.
Evidence indicates that STAT3 participates in the initiation and progression of lung cancer during cell proliferation, apoptosis and migration; however, whether and how TP affects STAT3 and its targets remain unclear.
In addition, gene knockdown and RNAseq were used to investigate molecular mechanisms through which STAT3 regulates tumor progression and the survival in lung cancer.
The identification of a miR-337-3p as a modulator of cellular response to taxanes, and STAT3 and RAP1A as regulatory targets which mediate that response, defines a novel regulatory pathway modulating paclitaxel sensitivity in lung cancer cells, which may provide novel adjuvant strategies along with paclitaxel in the treatment of lung cancer and may also provide biomarkers for predicting paclitaxel response in NSCLC.
Given that the activation of STAT3 is observed in nearly 50% of Lung cancers and more and more researches regarding STAT3 in tumors, here in, we reviewed the contribution of STAT3 to lung cancer growth and progression and then the context in which positive and negative regulation of STAT activation leading to cell competition provides a mechanism for therapeutic intervention for specific cancers is discussed.
Persistently activated IL-6/STAT3 pathway promotes acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC) treatment. miR-206 has been verified to be dysregulated and plays as a negative regulator in lung cancer.
A group of Stat3 downstream genes were identified by Affymetrix GeneChip microarray analysis that can be used as biomarkers for lung cancer diagnosis and prognosis.