ABSTRACT
Nuclear factor 45 (NF-45) has been found to be markedly upregulated in several cancers, including esophageal squamous cell carcinoma (ESCC). However, the molecular mechanisms underlying its functions remain unclear. In this study, we confirm that overexpression of NF45 was frequently detected in ESCC tissues and was associated with poor outcome. Overexpression studies revealed that NF-45 promoted cell growth and invasion and upregulated Rac1/Tiam1 signalling via 14-3-3ε protein in ESCC cell lines. This novel mechanism linking upregulated NF45 expression to increased 14-3-3ε/Rac1/Tiam1 signalling and subsequent growth and invasion in ESCC may aid in identification of new therapeutic targets for this disease.
Subject(s)
14-3-3 Proteins/metabolism , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Neoplasm Invasiveness , Nuclear Factor 45 Protein/physiology , rac1 GTP-Binding Protein/metabolism , Carcinoma, Squamous Cell/metabolism , Cell Proliferation , Esophageal Neoplasms/metabolism , Female , Humans , Male , Middle Aged , Prognosis , Signal Transduction , T-Lymphoma Invasion and Metastasis-inducing Protein 1/metabolismABSTRACT
[Objective]To observe the biological characteristics of CD133 positive cells derived from cutaneous squa-mous cell carcinoma(cSCC),and to investigate the mechanism of self-renewal of cancer stem cells(CSC)and the malig-nant behavior in cSCC.[Methods]The flow cytometry was applied to purify CD133+cells and CD133-from cutaneous squa-mous cell carcinoma cell line Colo-16.The effects of CD133 on the cell proliferative,self renew and migratory activity of two group cells were detected by MTT assay,Sphere formation assay and Transwell assay.Western blot and quantitative flu-orescent PCR were performed to investigate the expression of cancer stem cell associated gene CD44,OCT4 and SOX2 in two groups of cells.Examined the expression level of CD133 in actinic keratosis,squamous cell carcinoma in situ and cSCC by immunohistochemistry.[Result]The CD133+Colo-16 cells exhibited significantly stronger proliferation,self-renewal and metastasis ability(P<0.05)and present higher level protein and mRNA expression on CD44,SOX2 and OCT4(P<0.05). In addition,the expression level of CD133 was dynamic rise during the continuous evolution of actinic keratosis,squamous cell carcinoma in situ and cSCC.[Conclusions]The expression level of CD133 may be related to the tumorigenesis of cSCC and the malignant behavior including proliferative,self renew and migratory activity,and CD133+cSCC cells show the properties of cancer stem cells.The occurrence and development of cSCC may be related to the CSC,which express CD133.
ABSTRACT
Partitioning defective protein 3 (Par3) can activate the Tiam1/Rac pathway to inhibit invasion and metastasis in many cancers; however, the role of Par3 in lung adenocarcinoma remains unknown. Here we show that Par3 is downregulated in lung adenocarcinoma tissues and is associated with higher rates of lymph node metastasis and recurrence. Our functional study demonstrated that knock-down of Par3 promoted lung adenocarcinoma cell growth, cell migration, tumor formation, and metastasis, all of which were effectively inhibited when 14-3-3ζ was silenced. We found that Par3 binded with 14-3-3ζ protein and also showed that Par3 abrogated the binding of 14-3-3ζ to Tiam1, which was responsible for Rac1 activation. Knock-down of 14-3-3ζ inhibited Tiam1/Rac-GTP activation and blocked the invasive behavior of cells lacking Par3. These data suggest that loss of Par3 promotes metastatic behavior in lung adenocarcinoma cells through 14-3-3ζ protein.
Subject(s)
14-3-3 Proteins/metabolism , Adenocarcinoma/metabolism , Cell Cycle Proteins/metabolism , Cell Movement , Lung Neoplasms/metabolism , Membrane Proteins/metabolism , 14-3-3 Proteins/genetics , A549 Cells , Adaptor Proteins, Signal Transducing , Adenocarcinoma/genetics , Adenocarcinoma/secondary , Adenocarcinoma of Lung , Animals , Cell Cycle Proteins/genetics , Cell Proliferation , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Membrane Proteins/genetics , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Neovascularization, Pathologic , Protein Binding , RNA Interference , Signal Transduction , T-Lymphoma Invasion and Metastasis-inducing Protein 1/metabolism , Transfection , Tumor Burden , rac1 GTP-Binding Protein/metabolismABSTRACT
<p><b>OBJECTIVE</b>To study the effects of long-term exposure to carbon disulfide (SC(2)) on cardiovascular system of workers.</p><p><b>METHODS</b>The concentrations of CS(2) were detected in the representative workshops with different exposure levels. The indicators related to cardiovascular system were tested in 633 workers occupationally exposed to CS(2), which included blood pressure, electrocardiogram, blood routine (blood RT), cholesterol (TCHO), triglyceride (TG) and so on. The data were analyzed by chi-square test and multiple logistic regression analysis.</p><p><b>RESULTS</b>The exposure concentration of CS(2) for 389 workers was less than or equal to 5 mg/m(3), which for other 244 workers was higher than 5 mg/m(3). The maximum exposure concentration of CS(2) was 15.73 mg/m(3). There were no significant effects of CS(2) on the electrocardiogram, red blood cells, white blood cells, blood platelet, TCHO and TG of workers. However, the positive effects of CS(2) on blood pressure and negative effects of CS(2) on hemoglobin were found. The rates of high TCHO, TG and hypertension in male workers were significantly higher than those in female workers (P < 0.05). The rates of high TCHO, hypertension and sinus arrhythmia in older workers (≤ 30 years old) were significantly higher than those in young workers (> 30 years old) (P < 0.05). The rate of sinus arrhythmia in workers with 1 - 10 working years was significantly higher than that in workers with more than 10 working years (P < 0.05). The rate of hypertension in workers with 1 - 10 working years was significantly lower than that in workers with more than 10 working years (P < 0.05).</p><p><b>CONCLUSION</b>There were no significant effects of CS(2) exposure on the indexes of cardiovascular system of workers.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Blood Pressure , Carbon Disulfide , Cardiovascular System , Erythrocyte Count , Occupational Exposure , Risk FactorsABSTRACT
A fetal/maternal multi-parameter monitor is introduced here in the paper. It can monitor the vital signs of a fetus and his/her mother in a same screen synchronously. It is more useful in obstetric clinics. Its other functions include management of patient file, computer-assistant analyses.
