Activation of signal transducer and activator of transcription 3 (Stat3) pathway in osteosarcoma cells and overexpression of phosphorylated-Stat3 correlates with poor prognosis

2010 ◽  
Vol 28 (7) ◽  
pp. 971-978 ◽  
Author(s):  
Keinosuke Ryu ◽  
Edwin Choy ◽  
Cao Yang ◽  
Michiro Susa ◽  
Francis J. Hornicek ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Signal Transducer ◽  
Osteosarcoma Cells ◽  
Stat3 Pathway ◽  
Transcription 3 ◽  
Phosphorylated Stat3

scholarly journals Qizhufang (ZSF) Ameliorates Hepatic Iron Overload via Signal Transducer and Activator of Transcription 3 (STAT3) Pathway

2019 ◽  
Vol 25 ◽  
pp. 7836-7844
Author(s):  
Dongyu Xie ◽  
Haina Xie ◽  
Lin Liu ◽  
Guangwei Feng ◽  
Wenjing Jiang ◽  
...  
Keyword(s):  
Iron Overload ◽  
Hepatic Iron ◽  
Signal Transducer ◽  
Stat3 Pathway ◽  
Hepatic Iron Overload ◽  
Transcription 3

scholarly journals Cloning of porcine signal transducer and activator of transcription 3 cDNA and its expression in reproductive tissues

Reproduction ◽  
2006 ◽  
Vol 132 (3) ◽  
pp. 511-518 ◽  
Author(s):  
Lihua Wen ◽  
Jesse Craig ◽  
Paul W Dyce ◽  
Julang Li
Keyword(s):  
Growth Factor ◽  
Ovarian Function ◽  
Control Level ◽  
Signal Transducer ◽  
Rt Pcr ◽  
Western Blots ◽  
Epidermal Growth ◽  
Mucosal Folds ◽  
Transcription 3 ◽  
Phosphorylated Stat3

The signal transducer and activator of transcription 3 (Stat3) protein is a member of the Stat family that has a variety of biological functions including cell growth, anti-apoptosis, and cell motility, depending on the cell type and stimulus. Recent studies have suggested that Stat3 plays an important role in embryo development. Although the Stat3 gene has been cloned in humans, mice, cow, and rats, its sequence in pigs is unknown. In the present study, the 2476 bp Stat3 cDNA was cloned using real time reverse transcriptase (RT)-PCR. Comparison of sequences across species revealed that the porcine Stat3 cDNA is 93 and 90% homologous to human and mouse respectively. To study the expression pattern of Stat3, RNA and protein were isolated from heart, lung, kidney, ovary, oviduct, and uterus tissues. RT-PCR and western blot indicated that Stat3 is expressed in all the tissues tested, and the level of expression is relatively high in tissues from the reproductive system. In addition, immunohistochemistry studies suggested that the Stat3 protein was present in the oocyte, granulosa, theca, and interstitial cells of the ovary, the mucosal folds in the oviduct, and both the epithelium and stromal layers in the endometrium. To study whether Stat3 is functional in responding to growth factor stimulation in the ovary, granulosa cells were isolated from large follicles (>3 mm) and cultured in the presence of epidermal growth factor (EGF; 10 ng/ml) for 5, 10, 15, 30, and 60 min, following which western blots were performed using an antibody against the phosphorylated Stat3. Phosphorylated Stat3 was upregulated following 5 min of EGF challenge and was sustained during the 15-min stimulation, and decreased back to the control level following 60-min stimulation. The translocation of phosphorylated Stat3 from cytoplasm to nucleus following stimulation of EGF was also detected via immunocytochemistry. Our data suggests that Stat3 may play a role in porcine ovarian function.

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.

scholarly journals Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system

2014 ◽  
Vol 13 ◽  
pp. CIN.S12493 ◽  
Author(s):  
Li-Yu D. Liu ◽  
Li-Yun Chang ◽  
Wen-Hung Kuo ◽  
Hsiao-Lin Hwa ◽  
Yi-Shing Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Cancer Cell Line ◽  
Signal Transducer ◽  
Breast Cancers ◽  
Luminal A ◽  
Regulatory Pathways ◽  
Luminal B ◽  
Prognostic Features ◽  
Transcription 3

The aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis, primarily in estrogen receptor positive (ER(+)) breast cancers. Activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of STAT3 in ER(+) breast cancers are through multiple interacting regulatory pathways, including STAT3-MYC, STAT3-ERα, and STAT3-MYC-ERα interactions, as well as the direct action of activated STAT3. These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ERα and STAT3 in regulating their shared target gene-METAP2 is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients. VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model.

scholarly journals Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3

2016 ◽  
Vol 124 (5) ◽  
pp. 1310-1318 ◽  
Author(s):  
Zhaoxia Zou ◽  
Yufang Yin ◽  
Jenny Lin ◽  
Li-chen J. Hsu ◽  
Vanessa L. Brandon ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Murine Model ◽  
Signal Transducer ◽  
Convection Enhanced Delivery ◽  
Stat3 Pathway ◽  
Transcription 3 ◽  
Melanoma Cell Lines

OBJECT Despite recent advances, metastatic melanoma remains a terminal disease, in which life-threatening brain metastasis occurs in approximately half of patients. Sorafenib is a multikinase inhibitor that induces apoptosis of melanoma cells in vitro. However, systemic administration has been ineffective because adequate tissue concentrations cannot be achieved. This study investigated if convection-enhanced delivery (CED) of sorafenib would enhance tumor control and survival via inhibition of the signal transducer and activator of transcription 3 (Stat3) pathway in a murine model of metastatic brain melanoma. METHODS Melanoma cells treated with sorafenib in vitro were examined for signaling and survival changes. The effect of sorafenib given by CED was assessed by bioluminescent imaging and animal survival. RESULTS The results showed that sorafenib induced cell death in the 4 established melanoma cell lines and in 1 primary cultured melanoma cell line. Sorafenib inhibited Stat3 phosphorylation in HTB65, WYC1, and B16 cells. Accordingly, sorafenib treatment also decreased expression of Mcl-1 mRNA in melanoma cell lines. Because sorafenib targets multiple pathways, the present study demonstrated the contribution of the Stat3 pathway by showing that mouse embryonic fibroblast (MEF) Stat3 +/+ cells were significantly more sensitive to sorafenib than MEF Stat3 −/− cells. In the murine model of melanoma brain metastasis used in this study, CED of sorafenib increased survival by 150% in the treatment group compared with animals receiving the vehicle control (p < 0.01). CED of sorafenib also significantly abrogated tumor growth. CONCLUSIONS The data from this study indicate that local delivery of sorafenib effectively controls brain melanoma. These findings validate further investigation of the use of CED to distribute molecularly targeted agents.

Abstract 349: Signal Transducer and Activator of Transcription 3 (Stat3) in the Matrix of Cardiomyocyte Mitochondria

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kerstin Boengler ◽  
Ina Konietzka ◽  
Anita van de Sand ◽  
Denise Hilfiker-Kleiner ◽  
Gerd Heusch ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Western Blot ◽  
Outer Membrane ◽  
Confocal Laser ◽  
Signal Transducer ◽  
Confocal Laser Scan Microscopy ◽  
Marker Proteins ◽  
The Matrix ◽  
Transcription 3 ◽  
Phosphorylated Stat3

STAT3 (signal transducer and activator of transcription 3) transduces signals from the plasma membrane to the nucleus and is central for the cardioprotection by ischemic pre- and postconditioning. However, preliminary data suggest that STAT3 is also located in mitochondria. The aim of the present study was to confirm the presence of STAT3 in cardiomyocyte mitochondria, to elucidate its submitochondrial localization and to identify interacting proteins and the import mechanism of STAT3. STAT3 was detected by Western blot analysis in mitochondrial preparations from rat left ventricle (LV), which were negative for marker proteins of other subcellular compartments (sarcolemma, sarcoplasmic reticulum, nucleus, and cytosol). This finding was confirmed by confocal laser scan microscopy on mouse LV mitochondria (n=4). In contrast, no STAT3 was detected in mitochondria isolated from the LV of mice with a cardiomyocyte-specific deletion of STAT3 (n=3). Immunoprecipitation and confocal laser scan microscopy showed that, apart from total STAT3, also Ser727- and Tyr705-phosphorylated STAT3 was present in rat mitochondria. The analysis of subfractionated mitochondria by Western blot displayed STAT3 predominantly in the fraction negative for marker proteins of the outer membrane (voltage dependent anion channel), inner membrane (ATP synthase alpha), and the intermembrane space (cytochrome c), but positive for marker proteins of the matrix such as cyclophilin D (n=4). Immunoprecipitation of STAT3 from right ventricular and mitochondrial proteins showed a co-precipitation of connexin 43 (Cx43), which is present both at the sarcolemma and at the inner mitochondrial membrane and is also involved in cardioprotection, but not with GSK3β, MnSOD or cytochrome c. Furthermore, STAT3 co-precipitated with Tom20 (translocase of the outer membrane 20), which regulates the import of proteins into the mitochondria. Taken together, total and phosphorylated STAT3 are present in the matrix of cardiomyocyte mitochondria, STAT3 is possibly imported via a Tom20-dependent pathway, and STAT3 interacts with mitochondrial Cx43, and is thus possibly involved in Cx43-mediated cardioprotection.

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