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.
We showed that miR-1207-5p inhibited lung cancer cell A549 proliferation, migration and invasion in vitro, and suppressed the STAT3 and AKT signalings. miR-1207-5p overexpression can increase HUVEC angiogenesis, and can modulate the M2 phenotype of macrophage. miR-1207-5p also significantly inhibited A549 cells metastasis in a nude mouse xenograft model. miR-1207-5p and CSF1 expression levels and their relationship with lung cancer survival and metastasis status were assayed by means of a lung cancer tissue microarray.
We investigated the time-dependent PIAS3 shuffling and binding to STAT3 in an EGF-dependent model in lung cancer by using confocal microscopy, immunoprecipitation, luciferase reporter assay, and protein analysis of segregated cellular components.
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.
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.
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).
We found that paclitaxel activated Stat3 in the human lung cancer cell lines PC14PE6AS2 (AS2) and H157, whereas it reduced Stat3 activation in A549 and H460 cells.
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 examined IL-6/STAT3 in lung cancer tumor tissues and the effects of siltuximab, a neutralizing antibody to human IL-6, in mouse models of lung cancer.
Using conditioned medium (CM) derived from SLF to culture LC cells, the LC cells show obvious increase of viability and migration rates, significant increase expression of p-STAT3 and α-SMA, and decrease expression of P53 and E-cadherin.
To explore AG490 (the inhibitor of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway) in cisplatin (DDP)-induced acute kidney injury (AKI) in mice with lung cancer.
These findings uncover a novel mechanism of erlotinib resistance and provide a novel approach to overcome resistance by blocking the STAT3/Bcl2/Bcl-XL survival signaling pathway in human lung cancer.
The present study aimed to characterize the suppressive role of LLL12, a STAT3 small molecule inhibitor, in lung cancer cell proliferation and tumor growth.
The present results indicated that Ser44 and Ser120 sites of Nm23-H1 may be responsible for its biological suppressive effects of STAT3 and tumor metastasis, which may contribute to illuminate the metastasis suppression function of Nm23-H1 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.
Taken together, mir-125a-5p inhibited the proliferation and invasion of lung cancer cells and facilitated lung cancer cell apoptosis through suppressing STAT3.
Systemic delivery of the unformulated ASO, AZD9150, decreased STAT3 expression in a broad range of preclinical cancer models and showed antitumor activity in lymphoma and lung cancer models.