Search results for "STAT3"

The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide synthase in human colon carcinoma cells.

2007

Inducible nitric-oxide synthase (iNOS) has been identified as a marker and mediator of disease in human colonic inflammation and carcinogenesis. Accordingly, identification of mediators that trigger iNOS in colon carcinoma/epithelial cells is an important topic of current research. Here we demonstrate that interleukin (IL)-22, a newly described member of the IL-10 cytokine family, potently synergizes with interferon (IFN)-gamma for iNOS expression in human DLD-1 colon carcinoma cells. Detection of both IL-22 receptor chains and STAT3 phosphorylation proved robust IL-22 responsiveness of these cells. Short interfering RNA technology identified STAT3 as being crucial for up-regulation of iNOS…

Tristetraprolin regulation of interleukin-22 production

2015

AbstractInterleukin (IL)-22 is a STAT3-activating cytokine displaying characteristic AU-rich elements (ARE) in the 3′-untranslated region (3′-UTR) of its mRNA. This architecture suggests gene regulation by modulation of mRNA stability. Since related cytokines undergo post-transcriptional regulation by ARE-binding tristetraprolin (TTP), the role of this destabilizing protein in IL-22 production was investigated. Herein, we demonstrate that TTP-deficient mice display augmented serum IL-22. Likewise, IL-22 mRNA was enhanced in TTP-deficient splenocytes and isolated primary T cells. A pivotal role for TTP is underscored by an extended IL-22 mRNA half-life detectable in TTP-deficient T cells. Lu…

Leptin and Its Receptor are Overexpressed in Brain Tumors and Correlate with the Degree of Malignancy

2009

Although leptin and its receptor (ObR) have emerged as important cancer biomarkers, the role of the leptin system in brain tumor development remains unknown. We screened 87 human brain tumor biopsies using immunohistochemistry and detected leptin and ObR in 55.2% and 60.9% cases, respectively. In contrast, leptin and ObR were absent in 14 samples of normal brain tissue. The presence of leptin correlated with ObR with overall concordance 80.5%. The leptin/ObR system was highly expressed in glioblastomas and anaplastic astrocytomas, while lower expression of both markers was noted in low-grade astrocytomas and gangliogliomas. The association between leptin/ObR and the degree of tumor malignan…

PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion.

2015

Abstract Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the cell polarity regulator PARD3 to the development of lung squamous cell carcinomas (LSCC). Tumor-specific PARD3 alterations were found in 8% of LSCCs examined, placing PARD3 among the most common tumor suppressor genes in this malignancy. Most PAR3-mutant proteins exhibited a relative reduction in the ability to mediate formation of tight junctions and actin-based protrusions, bind atypical protein kinase C, activate RAC1, and activate STAT3 at cell confluence. Thus, PARD3 alterations prevented the formation of c…

Novel Signal Transduction Pathways: Analysis of STAT-3 and Rac-1 Signaling in Inflammatory Bowel Disease

2006

Although the precise etiology of inflammatory bowel disease still remains unclear, considerable progress has been made in the identification of novel signal transduction pathways that elucidate the immunopathogenesis involved in the perpetuation of the inflammatory process. Augmented T cell resistance against apoptosis is regarded as a pivotal factor in the pathogenesis, as it impairs mucosal homeostasis and leads to unrestrained accumulation of activated T cells, which subsequently lead to the amplification of the inflammatory response. Therefore novel therapeutic strategies aim at restoring mucosal T cell susceptibility to apoptosis through targeting of signal transduction pathways that a…

HSP110 : role in colorectal cancer development and immunogenicity

2015

Our team studies HSPs, including HSP110. HSPs are chaperones involved in the folding of newly synthesized and denatured proteins. HSPs are overexpressed under stress conditions and are involved in cell survival thanks to their anti-apoptotic and anti-aggregation functions. HSP110 is overexpressed in colorectal cancer and is associated with a poor prognosis. The expression of a mutant HSP110, named HSP110DE9, has been shown in MSI colorectal cancer. This one was shown to act there as a dominant negative, by binding HSP110 and inhibiting its functions. Its expression sensitizes cancer cells to chemotherapy and is associated with a better prognosis for patients.I was first interested in HSP110…

Expression of angiogenic regulators. VEGF and leptin, is regulated by the EGF/P13K/STAT3 pathway in colorectal cancer cells

2009

STAT3 activation: A key factor in tumor immunoescape.

2012

Cancer growth is controlled by cancer cells (cell intrinsic phenomenon), but also by the immune cells in the tumor microenvironment (cell extrinsic phenomenon). Thus cancer progression is mediated by the activation of transcription programs responsible for cancer cell proliferation, but also induced proliferation/activation of immunosuppressive cells such as Th17, Treg or myeloid derived suppressor cells (MDSCs). One of the key transcription factors involved in these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on STAT3 activation in immune cells, and how it impacts on tumor progression.

The designer cytokine hyper-interleukin-6 is a potent activator of STAT3-dependent gene transcription in vivo and in vitro.

1999

Interleukin-6 (IL-6) triggers pivotal pathways in vivo. The designer protein hyper-IL-6 (H-IL-6) fuses the soluble IL-6 receptor (sIL-6R) through an intermediate linker with IL-6. The intracellular pathways that are triggered by H-IL-6 are not defined yet. Therefore, we studied the molecular mechanisms leading to H-IL-6-dependent gene activation. H-IL-6 stimulates haptoglobin mRNA expression in HepG2 cells, which is transcriptionally mediated as assessed by run-off experiments. The increase in haptoglobin gene transcription correlates with higher nuclear translocation of tyrosine-phosphorylated STAT3 and its DNA binding. As H-IL-6 stimulates STAT3-dependent gene transcription, we compared t…

The role of NFkappaB inducing kinase (NIK) in the pathogenicity of EAE

2014

pathways (PTPN6, SLC3A2, VAV3, DDR1) and modulators of oxidative stress (MT1A, HMOX1, SLC30A1) were also significantly affected by the CBD treatment. The microarray results were confirmed using qPCR on selected gene targets. Immunoblotting demonstrated that CBD reduces IL-17 by decreasing STAT3 phosphorylation and increasing that of STAT5. In conclusion, our observations increase our understanding of the mechanisms of the anti-inflammatory activities of CBD.