STAT3 as a prognostic marker in human gastric cancer

Jackson, Christopher J.; Giraud, Andrew S.

doi:10.1111/j.1440-1746.2009.05822.x

Cited by 34 publications

(19 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To address such a possibility, we examined the inhibitory effect of niditine chloride on STAT3 in 2 human gastric cancer cell lines, SGC-7901 and AGS, which are known to express constitutively active STAT3 protein (31,32). As expected, nitidine chloride blocked STAT3 phosphorylation in SGC-7901 cancer cells in dose-and time-dependent manners in both whole-cell lysate (Fig.…”

Section: Nitidine Chloride Suppresses Stat3 Signaling In Gastric Cancmentioning

confidence: 99%

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Chen

Wang

Lin

et al. 2012

Molecular Cancer Therapeutics

137

122

View full text Add to dashboard Cite

STAT3 has been strongly implicated in human malignancies, and constitutive activation of STAT3 serves a crucial role in cell survival, angiogenesis, immune evasion, and inflammation. In this study, we showed that nitidine chloride, a natural phytochemical alkaloid derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through STAT3 signaling cascade. Nitidine chloride dose dependently suppressed VEGFinduced endothelial cell proliferation, migration, and tubular structure formation in vitro and dramatically reduced VEGF-triggered neovascularization in mouse cornea and Matrigel plugs in vivo. This angiogenesis inhibition mediated by nitidine chloride was well interpreted by the suppression of Janus kinase 2/STAT3 signaling and STAT3 DNA-binding activity in endothelial cells. Furthermore, nitidine chloride suppressed the constitutively activated STAT3 protein, its DNA-binding activity, and the expression of STAT3-dependent target genes, including cyclin D1, Bcl-xL, and VEGF in human gastric cancer cells. Consistent with the earlier findings, nitidine chloride inhibited gastric tumor cell growth and induced tumor cell apoptosis in vitro and effectively suppressed the volume, weight, and microvessel density of human SGC-7901 gastric solid tumors (n ¼ 8) at a dosage of 7 mg/kg/d (intraperitoneal injection). Immunohistochemistry and Western blot analysis further revealed that the expression of STAT3, CD31, and VEGF protein in xenografts was remarkably decreased by the alkaloid. Taken together, we propose that nitidine chloride is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor. Mol Cancer Ther; 11(2); 277-87. Ó2011 AACR.

show abstract

Section: Nitidine Chloride Suppresses Stat3 Signaling In Gastric Cancmentioning

confidence: 99%

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Chen

Wang

Lin

et al. 2012

Molecular Cancer Therapeutics

137

122

View full text Add to dashboard Cite

show abstract

“…The regulation of STAT3 by IL-6 has received considerable attention in the study of both cancer biology and (auto)immunity, and pathway signatures that reflect altered STAT3 activity have prognostic value in certain cancers (4,(110)(111)(112). Furthermore, pharmacogenomic approaches have identified genetic links between STAT3 and chronic disease.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…For example, in hepatocellular adenoma, somatic mutations coding for constitutively activated gp130 have been detected (107), while elevated IL-6 levels in patients with breast, lung, and hematopoietic tumors correlate with poor clinical outcome (108,109). Biomarkers of STAT3 activity also represent reliable diagnostic/prognostic factors for patients with colorectal neoplasia and non-small cell lung carcinoma (100,(110)(111)(112). Furthermore, ADAM17, which mediates the ectodomain shedding (and activation) of some EGFR ligands, Notch and IL-6R, is also upregulated in various cancers (113) and is considered a novel anticancer drug target (114).…”

Section: Figurementioning

confidence: 99%

Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling

Jones

Scheller²,

Rose-John³

2011

J. Clin. Invest.

615

555

View full text Add to dashboard Cite

“…Alteration of the PI3K/Akt/mTOR pathway has been frequently detected in gastric carcinoma [6][7][8], indicating a potential signaling pathway target for efficacious treatment of GC. In gastric carcinogenesis, STAT3 is activated and functions as a transcription factor that induces a host of target genes, involving those involved in cell proliferation, invasion/ metastasis, and angiogenesis [9,10]. A recent notable study provided a more comprehensive molecular evaluation of primary gastric adenocarcinoma tissues [11].…”

Section: Introductionmentioning

confidence: 99%

Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5

Qiao

Gong

Song

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: PITX1 has been identified as a potential tumor-suppressor gene in several malignant tumors. The molecular mechanism underlying PITX1, particularly its function as a transcription factor regulating gene expression during tumorigenesis, is still poorly understood. Methods: The expression level and location of PITX1 were determined by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical staining in gastric cancer (GC). The effect of PITX1 on the GC cell proliferation and tumorigenesis was analyzed in vitro and in vivo. To explore how PITX1 suppresses cell proliferation, we used PITX1-ChIP-sequencing to measure genome-wide binding sites of PITX1 and assessed global function associations based on its putative target genes. ChIP-PCR, electrophoretic mobility shift assay, and promoter reporter assays examined whether PITX1 bound to PDCD5 and regulated its expression. The function of PDCD5 in GC cell apoptosis was further examined in vitro and in vivo. The relationship between the PITX1 protein level and GC patient prognosis was evaluated by the Kaplan-Meier estimator. Meanwhile, the expression level of miR-19a-3p, which is related to PITX1, was also detected by luciferase reporter assay, qRT-PCR, and western blotting. Results: The expression level of PITX1 was decreased in GC tissues and cell lines. Elevated PITX1 expression significantly suppressed the cell proliferation of GC cells and tumorigenesis in vitro and in vivo. PITX1 knockdown blocked its inhibition of GC cell proliferation. PITX1 bound to whole genomewide sites, with these targets enriched on genes with functions mainly related to cell growth and apoptosis. PITX1 bound to PDCD5, an apoptosis-related gene, during tumorigenesis, and cis-regulated PDCD5 expression. Increased PDCD5 expression in GC cells not only induced GC cell apoptosis, but also suppressed GC cell growth in vitro and in vivo. Moreover, PITX1 expression was regulated by miR-19a-3p. More importantly, a decreased level of PITX1 protein was correlated with poor GC patient prognosis. Conclusion: Decreased expression of PITX1 predicts shorter overall survival in GC patients. As a transcriptional activator, PITX1 regulates apoptosis-related genes, including PDCD5, during gastric carcinogenesis. These data indicate PDCD5 to be a novel and feasible therapeutic target for GC.

show abstract

STAT3 as a prognostic marker in human gastric cancer

Cited by 34 publications

References 22 publications

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling

Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5

Contact Info

Product

Resources

About