We found that antitumor type 1 CD4<sup>+</sup> T-helper (Th1) cells and CD8<sup>+</sup> T cells were directly counter balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8<sup>+</sup> T cells, enhancement of cytotoxicity toward CD4<sup>+</sup> and CD8<sup>+</sup> T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DC), and polarization of macrophages toward the M2 phenotype.
We uncovered signaling mediated by Janus kinases (Jaks) and the transcription factor Stat3 as a critical, pharmacologically targetable effector of CD109-driven lung cancer metastasis.
Reduced IL-6 levels and tumor-associated phospho-STAT3 are associated with reduced tumor development in a mouse model of lung cancer chemoprevention with myo-inositol.
In this study, the effects of chemically modified anti-STAT3 small interfering (si)RNAs on cell viability, proliferation and apoptosis of parental and cisplatin resistant non-small cell lung cancer (NSCLC) cells were investigated with the aim to provide a new therapeutic strategy for overcoming cisplatin resistance in lung cancer.
Moreover, exogenous IL-6 treatment stimulated Stat3 activation, enhanced TGF-β-induced expression of p-Smad3 and Snail, aggravated the EMT process, and increased lung cancer cell migration and invasion induced by TGF-β1.
We have found that signal transducer and activator of transcription 3 (Stat3) activation up-regulates ERβ expression in PC14PE6/AS2 lung cancer cells in a preliminary Affymetrix oligonucleotide array study, and we sought to confirm the findings.
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.
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.
Overall, our results elucidated a crucial role of LDOC1 in lung cancer and revealed how LDOC1 acts as a bridge between tobacco exposure and the IL-6/JAK2/STAT3 loop in this human malignancy.
Moreover, in a mouse lung cancer xenograft model, RES significantly inhibited the tumor growth, which was associated with inhibition of cell proliferation and decreased expression of p-STAT3 in tumor tissues.
Osteopontin production by TM4SF4 signaling drives a positive feedback autocrine loop with the STAT3 pathway to maintain cancer stem cell-like properties in lung cancer cells.
We further demonstrate that <i>PTPRT</i> promoter methylation associated with different levels of pSTAT3<sub>Ty705</sub> in lung cancer cell lines had selective sensitivity to STAT3 pathway small molecule inhibitors (SID 864,669 and SID 4,248,543).
Importantly, we demonstrated that BBR was able to inhibit doxorubicin (DOX)-mediated STAT3 activation and sensitize lung cancer cells to the cytotoxic effect of DOX treatment.