Search results for " Transcription factor"
showing 10 items of 656 documents
Suppressor of cytokine signaling 3 sensitizes anaplastic thyroid cancer to standard chemotherapy
2009
We previously showed that cancer cells from papillary, follicular, and anaplastic thyroid carcinomas produce interleukin-4 and interleukin-10, which counteract the cytotoxic activity of conventional chemotherapy through the up-regulation of antiapoptotic molecules. Here, we identify Janus kinase/signal transducers and activators of transcription (STAT) and phosphatidyl inositol 3-kinase (PI3K)/AKT as the down-stream pathways through which these cytokines confer resistance to cell death in thyroid cancer. We found that the absence of suppressors of cytokine signaling (SOCS) molecules allows the propagation of the survival signaling. Exogenous expression of SOCS1, SOCS3, and SOCS5 in the high…
Osteopontin shapes immunosuppression in the metastatic niche.
2014
Abstract The matricellular protein osteopontin (OPN, Spp-1) is widely associated with cancer aggressiveness when produced by tumor cells, but its impact is uncertain when produced by leukocytes in the context of the tumor stroma. In a broad study using Spp1−/− mice along with gene silencing in tumor cells, we obtained evidence of distinct and common activities of OPN when produced by tumor or host cells in a spontaneously metastatic model of breast cancer. Different cellular localization of OPN is associated with its distinct activities, being mainly secreted in tumor cells while intracellular in myeloid cells. OPN produced by tumor cells supported their survival in the blood stream, wherea…
Parthenolide sensitizes hepatocellular carcinoma cells to trail by inducing the expression of death receptors through inhibition of STAT3 activation
2011
This article shows that HepG2, Hep3B, and SK-Hep1 cells, three lines of human hepatocellular carcinoma (HCC) cells, are resistant to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Parthenolide, a sesquiterpene lactone found in European feverfew, has been shown to exert both anti-inflammatory and anti-cancer activities. This article demonstrates that co-treatment with parthenolide and TRAIL-induced apoptosis with synergistic interactions in the three lines of HCC cells. In order to explain these effects we ascertained that parthenolide increased either at protein or mRNA level the total content of death receptors TRAIL-R1 and -R2 as well as their surfac…
Shikonin promotes intestinal wound healing in vitro via induction of TGF-β release in IEC-18 cells
2013
The intestinal barrier is a complex system with a dynamic structure that is designed for the maintenance of homeostasis in healthy individuals. Ulcerative colitis, one of the main manifestations of inflammatory bowel disease, is characterized by an inadequate and delayed wound healing. Shikonin, the active principle in the root of Lithospermum erythrorhizon, has demonstrated its ability to attenuate dextran sulfate sodium-induced ulcerative colitis in mice. Moreover, the root of L. erythrorhizon has been used in traditional Chinese medicine for treatment of burns, anal ulcers, hemorrhoids and skin wounds. However, the effect of shikonin on intestinal wound healing is unknown. Using an in vi…
Signaling molecules: the pathogenic role of the IL-6/STAT-3 trans signaling pathway in intestinal inflammation and in colonic cancer.
2008
Although the precise etiology of inflammatory bowel diseases (IBD) 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. As both ulcerative colitis and Crohn's disease are associated with an increased risk for developing colorectal cancer (CRC) and precancerous dysplastic epithelial changes, further studies have concentrated on finding a common signaling pathway that could serve as a mechanistic link between inflammation and associated colonic cancer in IBD. This review presents the current data concerning the pathogenic role of the…
Effect of LIF-withdrawal on acetylcholine synthesis in the embryonic stem cell line CGR8 is not mediated by STAT3, PI3Ks or cAMP/PKA pathways.
2015
Acetylcholine (ACh) acts as a local cellular signaling molecule and is widely expressed in nature, including mammalian cells and embryonic stem cells. The murine embryonic stem cell line CGR8 synthesizes and releases substantial amounts of ACh. Particularly during early differentiation - a period associated with multiple alterations in geno-/phenotype functions - synthesis and release of ACh are increased by 10-fold. In murine stem cells second messengers of the STAT-3, PI3K and cAMP/PKA pathways are involved in maintaining self-renewal and pluripotency. The present experiments were designed to test whether blockers of these signaling pathways enhance ACh cell content in the presence of LIF…
Activation of Intestinal Epithelial Stat3 Orchestrates Tissue Defense during Gastrointestinal Infection
2015
Gastrointestinal infections with EHEC and EPEC are responsible for outbreaks of diarrheal diseases and represent a global health problem. Innate first-line-defense mechanisms such as production of mucus and antimicrobial peptides by intestinal epithelial cells are of utmost importance for host control of gastrointestinal infections. For the first time, we directly demonstrate a critical role for Stat3 activation in intestinal epithelial cells upon infection of mice with Citrobacter rodentium - a murine pathogen that mimics human infections with attaching and effacing Escherichia coli. C. rodentium induced transcription of IL-6 and IL-22 in gut samples of mice and was associated with activat…
The antitumor activities of curcumin and its isoxazole analogue are not affected by multiple gene expression changes in an MDR model of the MCF-7 bre…
2007
We examined the effects of curcumin and of its isoxazole analogue MR 39 in the MCF-7 breast cancer cell line and in its multidrug-resistant (MDR) variant MCF-7R. In comparison with MCF-7, MCF-7R lacks estrogen receptor alpha (ERalpha) and overexpressess P-glycoprotein (P-gp), different IAPs (inhibitory of apoptosis proteins) and COX-2. Through analyses of the effects on cell proliferation, cycling and death, we have observed that the antitumor activity of curcumin and of the more potent (approximately two-fold) MR 39 is at least equal in the MDR cell line compared to the parental MCF-7. Similar results were observed also in an MDR variant of HL-60 leukemia. RT-PCR evaluations performed in M…
Cytoplasmic STAT proteins associate prior to activation
2000
The commonly accepted model of STAT factor activation at the cytoplasmic part of the receptor assumes that signal transducers and activators of transcription (STATs) are recruited from a cytoplasmic pool of monomeric STAT proteins. Based on a previous observation that non-phosphorylated STAT3-Src homology 2 domains dimerize in vitro, we investigated whether the observed dimerization is of physiological relevance within the cellular context. We show that STAT1 and STAT3 are pre-associated in non-stimulated cells. Apparently, these complexes are not able to translocate into the nucleus. We provide evidence that the event of STAT activation is more complex than previously assumed.
Socs3 induction by PPARγ restrains cancer-promoting inflammation
2013
The presence of proinflammatory cytokines in the tumor microenvironment can support further growth of established cancers. Docosahexaenoic acid (DHA), a peroxisome proliferator-activated receptor-gamma (PPARγ) ligand, has been shown to suppress inflammation and limit tumor progression in vivo. Are the anticancer properties of DHA relying on its ability to prevent inflammation? If so, what are the molecular links between the anti-inflammatory properties of DHA and its anticancer effects? DHA is an n-3 polyinsaturated fatty acid mainly found in fish oil that was shown to contribute to inflammation resolution by preventing the release of proinflammatory mediators in vivo.1 DHA has also been as…