6-OAP formed hydrogen bonds with Ser611/Ser613/Arg609 at the SH2 domain of STAT3 and inhibited the constitutive and interleukin-6-induced phosphorylated STAT3 (pSTAT3), leading to inhibitory effects on lung cancer cells and suppression of Skp2 transcription.
Stat3 downstream gene product chitinase 3-like 1 is a potential biomarker of inflammation-induced lung cancer in multiple mouse lung tumor models and humans.
Signal transducer and activator of transcription 3 (STAT3) activation is frequently found in human lung cancer and is associated with increased metastasis and reduced survival.
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.
STAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting STAT3 is currently proposed as therapeutic intervention.
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].
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.
Altogether, these results show T21 as a potent anticancer compound that effectively decreases survivin levels through STAT3 inhibition in lung cancer, appearing as a promising therapeutic drug for cancer treatment.
As a result, we found that microRNA-3127-5p promotes pSTAT3 to induce the expression of PD-L1; microRNA-3127-5p promotes STAT3 phosphorylation through suppressing autophagy, and autophagy could retaine pSTAT3 into the nucleus in miRNA-3127-5p knocked cells, and immune escape induced by elevated level of PD-L1 results in chemoresistance of lung cancer.
Collectively, these preclinical findings identify trans-signalling via STAT3 as the signalling modality by which IL-6 promotes muscle wasting in lung cancer cachexia, and therefore support the clinical evaluation of the IL-6 trans-signalling/STAT3 axis as a therapeutic target in advanced lung cancer patients presenting with cachexia.
Cooperative interaction between protein inhibitor of activated signal transducer and activator of transcription-3 with epidermal growth factor receptor blockade in lung cancer.