After adjusting for lung metastasis, stepwise logistic regression analysis revealed that the SNPs in signal transducer and activator 3 (STAT3) were most significantly associated with better response to IFN-alpha.
As shown by dominant-negative PDGF-R expression in these cells, ILEI-induced PDGF signaling was required for enhanced cell migration, nuclear accumulation of beta-catenin, nuclear pY-Stat3 and accelerated growth of lung metastases.
Four-fold fewer animals exhibited lung metastases in the absence of Stat3 and a 12-fold reduction in the number of lung lesions was observed in animals bearing Stat3-null tumors when compared with the wild-type cohort.
Furthermore, quercetin suppressed A375 tumor growth and STAT3 activities in xenografted mice model, and inhibited murine B16F10 cells lung metastasis in an animal model.
Here, we identify a miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer (NSCLC), independent of immunoinhibitory signals. miR-197 is downregulated in platinum-resistant NSCLC specimens, resulting in the promotion of chemoresistance, tumorigenicity, and pulmonary metastasis in vitro and in vivo.
Nude mice were injected intravenously with AGS cells treated with anti-Fas or treated with STAT3 inhibitor without anti-Fas; tumor pulmonary metastases were measured.
Taken together, AKT2 increases the migration and invasion of ovarian cancer cells in vitro and promotes lung metastasis in nude mice in vivo through PKM2-mediated elevation of STAT3 expression and NF-κB activation.
Importantly, metastatic lung colonization could be abrogated using an investigational drug that attenuates Stat3 activity, implicating this seed-and-soil interaction as a therapeutic target for eliminating lung metastasis.