scholarly journals P10.01 Anti-migration and anti-invasion effects of curcumin via suppression of fascin expression in glioblastoma cells

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii40-iii40
Author(s):  
P Ki-Su ◽  
S Yoon ◽  
J Hwang ◽  
H Ahn
Keyword(s):  
Western Blot ◽  
Tumor Cells ◽  
Natural Compound ◽  
Sandwich Elisa ◽  
Actin Binding ◽  
Migration And Invasion ◽  
Signal Transducer ◽  
Stat3 Phosphorylation ◽  
Transcription 3 ◽  
Invasion Assays

Abstract BACKGROUND The natural compound Curcumin was known to inhibit migration and invasion of glioblastoma (GBM) cells. Fascin, a kind of actin-binding proteins, is correlated with migration and invasion of GBM cells. The purpose of this study was to investigate anti-migration and anti-invasion effects of Curcumin via suppression of fascin expression in GBM cells. MATERIAL AND METHODS U87 cell line was used as an experimental model of GBM. Fascin was quantified by Western blot analysis. And, the signal transducer and activator of transcription 3 (STAT3), known to play an important role in migration and invasion of tumor cells, were analyzed by sandwich-ELISA. Migration and invasion capacities were assessed by attachment, migration and invasion assays. Cellular morphology was demonstrated by immunofluorescence. RESULTS At various concentrations of curcumin and exposure times, fascin expression decreased. After temporarily exposure to 10μM/L Curcumin during 6 hours as less invasive concentration and time, fascin expression temporarily decreased at 12 hours (18.4%, p=0.024), and since then recovered. And, the change of phosphrylated STAT3 level also reflected the temporarily decreased pattern of fascin expression at 12 hours (19.7%, p=0.010). Attachment, migration, and invasion capacities consistently decreased at 6, 12, and 24 hours. And, immunofluorescence showed the change of shape and the reduction of filopodia formation in cells. CONCLUSION Curcumin is likely to suppress the fascin expression in GBM cells, and this might be a possible mechanism for anti-migration and anti-invasion effects of Curcumin via inhibition of STAT3 phosphorylation.

scholarly journals Intranuclear Crosstalk between Extracellular Regulated Kinase1/2 and Signal Transducer and Activator of Transcription 3 Regulates JEG-3 Choriocarcinoma Cell Invasion and Proliferation

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Diana M. Morales-Prieto ◽  
Stephanie Ospina-Prieto ◽  
Wittaya Chaiwangyen ◽  
Maja Weber ◽  
Sebastian Hölters ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Capacity ◽  
Mapk Signaling ◽  
Signaling Molecules ◽  
Signal Transducer ◽  
Stat3 Phosphorylation ◽  
Functional Implications ◽  
Choriocarcinoma Cells ◽  
Cell Invasiveness ◽  
Transcription 3

Invasiveness of trophoblast and choriocarcinoma cells is in part mediated via leukemia inhibitory factor- (LIF-) induced activation of signal transducer and activator of transcription 3 (STAT3). The regulation of STAT3 phosphorylation at its ser727 binding site, possible crosstalk with intracellular MAPK signaling, and their functional implications are the object of the present investigation. JEG-3 choriocarcinoma cells were cultured in presence/absence of LIF and the specific ERK1/2 inhibitor (U0126). Phosphorylation of signaling molecules (p-STAT3 (ser727 and tyr705) and p-ERK1/2 (thr 202/tyr 204)) was assessed per Western blot. Immunocytochemistry confirmed results, but also pinpointed the location of phosphorylated signaling molecules. STAT3 DNA-binding capacity was studied with a colorimetric ELISA-based assay. Cell viability and invasion capability were assessed by MTS and Matrigel assays. Our results demonstrate that LIF-induced phosphorylation of STAT3 (tyr705 and ser727) is significantly increased after blocking ERK1/2. STAT3 DNA-binding capacity and cell invasiveness are enhanced after LIF stimulation and ERK1/2 blockage. In contrast, proliferation is enhanced by LIF but reduced after ERK1/2 inhibition. The findings herein show that blocking ERK1/2 increases LIF-induced STAT3 phosphorylation and STAT3 DNA-binding capacity by an intranuclear crosstalk, which leads to enhanced invasiveness and reduced proliferation.

scholarly journals Piwil2 Suppresses P53 by Inducing Phosphorylation of Signal Transducer and Activator of Transcription 3 in Tumor Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e30999 ◽  
Author(s):  
Yilu Lu ◽  
Kun Zhang ◽  
Chao Li ◽  
Youlin Yao ◽  
Dachang Tao ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Signal Transducer ◽  
Transcription 3

scholarly journals Increased Hypothalamic Signal Transducer and Activator of Transcription 3 Phosphorylation after Hindbrain Leptin Injection

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1509-1519 ◽  
Author(s):  
Marieke Ruiter ◽  
Patricia Duffy ◽  
Steven Simasko ◽  
Robert C. Ritter
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Leptin Receptor ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Solitary Tract ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation ◽  
Transcription 3

Reduction of food intake and body weight by leptin is attributed largely to its action in the hypothalamus. However, the signaling splice variant of the leptin receptor, LRb, also is expressed in the hindbrain, and leptin injections into the fourth cerebral ventricle or dorsal vagal complex are associated with reductions of feeding and body weight comparable to those induced by forebrain leptin administration. Although these observations suggest direct hindbrain action of leptin on feeding and body weight, the possibility that hindbrain leptin administration also activates the Janus kinase/signal transducer and activator of transcription 3 (STAT3) signaling in the hypothalamus has not been investigated. Confirming earlier work, we found that leptin produced comparable reductions of feeding and body weight when injected into the lateral ventricle or the fourth ventricle. We also found that lateral and fourth ventricle leptin injections produced comparable increases of STAT3 phosphorylation in both the hindbrain and the hypothalamus. Moreover, injection of 50 ng of leptin directly into the nucleus of the solitary tract also increased STAT3 phosphorylation in the hypothalamic arcuate and ventromedial nuclei. Increased hypothalamic STAT3 phosphorylation was not due to elevation of blood leptin concentrations and the pattern of STAT3 phosphorylation did not overlap distribution of the retrograde tracer, fluorogold, injected via the same cannula. Our observations indicate that even small leptin doses administered to the hindbrain can trigger leptin-related signaling in the forebrain, and raise the possibility that STAT3 phosphorylation in the hypothalamus may contribute to behavioral and metabolic changes observed after hindbrain leptin injections.

scholarly journals WW domain-containing E3 ubiquitin protein ligase 1 depletion evokes antitumor effect in cutaneous squamous cell carcinoma by inhibiting signal transducer and activator of transcription 3 signaling pathway

2018 ◽  
Vol 46 (7) ◽  
pp. 2898-2912 ◽  
Author(s):  
Yonghua Xia ◽  
Xiao Chang ◽  
Shi Lian ◽  
Wei Zhu
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Signal Transducer ◽  
Ubiquitin Protein Ligase ◽  
Transcription 3

Objectives WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) has been implicated in tumor progression. We aimed to investigate the role of WWP1 in cutaneous squamous cell carcinoma (CSCC). Methods WWP1 gene and protein levels were detected using semi-quantitative reverse transcription-polymerase chain reaction, immunohistochemistry and western blotting. The effects of WWP1 on cell cycle, apoptosis, cell migration and invasion were examined by flow cytometry, wound healing and Transwell assays, respectively. The antitumor efficacy of WWP1 small interfering RNA was determined in CSCC tumor xenografts in mice. Results WWP1 expression was significantly higher in CSCC tissues and cells than in normal skin and cells, respectively. WWP1 expression was significantly associated with histological grade, invasion depth and lymph node metastasis in patients with CSCC. High expression predicted metastatic potential and an unfavorable prognosis. WWP1 downregulation suppressed tumor growth in vitro and in vivo, reduced cell migration and invasion, arrested the cell cycle in G0/G1 and induced apoptosis in A431 cells. WWP1 depletion also decreased phosphorylated signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-2, cyclin D1 and Bcl-2, but did not affect total STAT3. Conclusions WWP1 is a potential target for the diagnosis, prognosis and therapy of patients with CSCC.

scholarly journals Verbascoside Inhibits Glioblastoma Cell Proliferation, Migration and Invasion While Promoting Apoptosis Through Upregulation of Protein Tyrosine Phosphatase SHP-1 and Inhibition of STAT3 Phosphorylation

2018 ◽  
Vol 47 (5) ◽  
pp. 1871-1882 ◽  
Author(s):  
Wei-Qiang Jia ◽  
Zhao-Tao Wang ◽  
Ming-Ming Zou ◽  
Jian-Hao Lin ◽  
Ye-Hai Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Western Blot ◽  
Protein Tyrosine Phosphatase ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Tyrosine Phosphatase ◽  
Migration And Invasion ◽  
Glioblastoma Cell ◽  
Stat3 Phosphorylation

Background/Aims: As a natural antioxidant, verbascoside (VB) is proved to be a promising method for the treatment of oxidative-stress-related neurodegenerative diseases. Thus, this study aimed to investigate the effects of VB on glioblastoma cell proliferation, apoptosis, migration, and invasion as well as the mechanism involving signal transducer and activator of transcription 3 (STAT3) and Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). Methods: U87 cells were assigned to different treatments. The MTT assay was used to test cell proliferation, flow cytometry was used to detect cell apoptosis, and a Transwell assay was used for cell migration and invasion. We analyzed the glioblastoma tumor growth in a xenograft mouse model. Western blot analysis was employed to determine the protein expression of related genes. Results: Glioblastoma cells exhibited decreased cell proliferation, migration, invasion, and increased apoptosis when treated with VB or TMZ. Western blot analysis revealed elevated SHP-1 expression and reduced phosphorylated (p)-STAT3 expression in glioblastoma cells treated with VB compared with controls. Correspondingly, in a xenograft mouse model treated with VB, glioblastoma tumor volume and growth were decreased. Glioblastoma xenograft tumors treated with VB showed elevated SHP-1, Bax, cleaved caspase-3, and cleaved PARP expression and reduced p-STAT3, Bcl-2, survivin, MMP-2, and MMP-9 expression. siRNA-SHP-1 inhibited the VB effects on glioblastoma. Conclusion: This study demonstrates that VB inhibits glioblastoma cell proliferation, migration, and invasion while promoting apoptosis via SHP-1 activation and inhibition of STAT3 phosphorylation.

scholarly journals Exploiting the STAT3 Nexus in Cancer-Associated Fibroblasts to Improve Cancer Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Amr Allam ◽  
Marina Yakou ◽  
Lokman Pang ◽  
Matthias Ernst ◽  
Jennifer Huynh
Keyword(s):  
Tumor Cells ◽  
Immune Suppression ◽  
Immune Cells ◽  
Therapeutic Benefit ◽  
Cancer Associated Fibroblasts ◽  
Signal Transducer ◽  
Growing Body ◽  
Heterogenous Population ◽  
Transcription 3 ◽  
Soluble Components

The tumor microenvironment (TME) is composed of a heterogenous population of cells that exist alongside the extracellular matrix and soluble components. These components can shape an environment that is conducive to tumor growth and metastatic spread. It is well-established that stromal cancer-associated fibroblasts (CAFs) in the TME play a pivotal role in creating and maintaining a growth-permissive environment for tumor cells. A growing body of work has uncovered that tumor cells recruit and educate CAFs to remodel the TME, however, the mechanisms by which this occurs remain incompletely understood. Recent studies suggest that the signal transducer and activator of transcription 3 (STAT3) is a key transcription factor that regulates the function of CAFs, and their crosstalk with tumor and immune cells within the TME. CAF-intrinsic STAT3 activity within the TME correlates with tumor progression, immune suppression and eventually the establishment of metastases. In this review, we will focus on the roles of STAT3 in regulating CAF function and their crosstalk with other cells constituting the TME and discuss the utility of targeting STAT3 within the TME for therapeutic benefit.

scholarly journals miR-384 targets metadherin gene to suppress growth, migration, and invasion of gastric cancer cells

2019 ◽  
Vol 47 (2) ◽  
pp. 926-935 ◽  
Author(s):  
Fang Wang
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Western Blot ◽  
Cell Lines ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cell Behaviors ◽  
Invasion Assays

Objective MicroRNA-384 (miR-384) has been reported to function as a tumor suppressor in multiple cancers; however, its role in gastric cancer (GC) remains unclear. Methods We measured expression levels of miR-384 in GC cell lines and in a normal gastric cell line (GES-1). The association between miR-384 and the metadherin gene ( MTDH) was assessed by luciferase reporter assay and western blot. The effects of the miR-384/MTDH axis on GC cell behaviors were measured by CCK-8, wound-healing, and transwell invasion assays. Results miR-384 was significantly downregulated in GC cell lines compared with normal gastric cells. MTDH was identified as a direct target of miR-384 by bioinformatics analysis, luciferase assay, and western blot. Functional assays demonstrated that miR-384 inhibited GC cell proliferation, migration, and invasion through targeting MTDH. Conclusion These results reveal that miR-384 acts as a tumor suppressor in GC and suggest that the miR-384/MTDH axis may be a potential therapeutic target for GC.

HDAC3 Silencing Enhances Acute B Lymphoblastic Leukaemia Cells Sensitivity to MG-132 by Inhibiting the JAK/Signal Transducer and Activator of Transcription 3 Signaling Pathway

Chemotherapy ◽  
2020 ◽  
Vol 65 (3-4) ◽  
pp. 85-100
Author(s):  
Yongling Guo ◽  
Xinyao Li ◽  
Zhengchang He ◽  
Dan Ma ◽  
Zhaoyuan Zhang ◽  
...  
Keyword(s):  
Western Blot ◽  
Therapeutic Strategy ◽  
Lymphocytic Leukaemia ◽  
Signal Transducer ◽  
Poor Survival ◽  
Stat3 Pathway ◽  
Cycle Arrest ◽  
M Phase ◽  
Interfering Rna ◽  
Transcription 3

<b><i>Purpose:</i></b> HDAC3, which is associated with smurf2, has been shown to be associated with poor prognosis in B-ALL. This study examined the efficacy of targeting HDAC3 combined with MG-132 as a possible therapeutic strategy for B-ALL patients. <b><i>Methods:</i></b> Real-time PCR and western blot were used to measure the expression of smurf2 and HDAC3 from B-ALL patients bone marrow samples. Sup-B15 and CCRF-SB cells were treated with MG-132, small interfering RNA of smurf2 or HDAC3. A plasmid designed to up-regulate smurf2 expression was transfected into B-ALL cells. Flow cytometry and western blot were used to measure variation due to these treatments in terms of apoptosis and cell cycle arrest. <b><i>Results:</i></b> Expression of Smurf2 and HDAC3 mRNA were inversely related in B-ALL patients. Up-regulation of smurf2 or MG-132 influenced HDAC3, further inhibiting the JAK/signal transducer and activator of transcription 3 (STAT3) signal pathway and inducing apoptosis in B-ALL cells. When we treated Sup-B15 and CCRF-SB cells with siHDAC3 and MG-132 for 24 h, silencing HDAC3 enhanced the apoptosis rate induced by MG-132 in B-ALL cells and further inhibited the JAK/STAT3 pathway. Furthermore, MG-132 was observed to cause G2/M phase arrest in B-ALL cells and inhibited the JAK/STAT3 pathway, leading to apoptosis. <b><i>Conclusions:</i></b> Silencing of HDAC3 enhanced the sensitivity of B-ALL cells to MG-132. The combination of targeting HDAC3 and MG-132 may provide a new avenue for clinical treatment of acute B lymphocytic leukaemia and improve the poor survival of leukaemia patients.

Sign in / Sign up

Export Citation Format

Share Document