Yi-Wen Wang

National Cheng Kung University, Tainan, Taiwan, Taiwan

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Publications (4)14.04 Total impact

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    ABSTRACT: Upper urinary tract (pyelocaliceal cavities and ureter) urothelial carcinoma (UUT-UC) is a relatively rare neoplastic disease. Although the diagnosis and treatment of this tumor variant have improved significantly, accurate risk stratification remains a challenge. To identify the putative oncogene involved in the progression of UC, a bioinformatics-guided experimental investigation was performed targeting on chromosome 19q13. The effects of EMP3 on cancer cell growth, migration, adhesion were investigated by transfection and siRNA experiments in vitro. The crosstalk of integrins or ErbB2 with EMP3 was examined by RT-PCR and immunoblotting. The potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was analyzed by methylation-specific PCR. To validate the clinical relevance, a cohort of UUT-UC (n = 77) was measured for EMP3 expression at mRNA and protein levels and compared for their prognostic significance in relation to ErbB2 expression. We showed a functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 overexpression promoted the proliferation and migration of cancer cells, but suppressed cell adhesion in vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in vitro. Kaplan-Meier survival estimates of clinical cohort showed that co-expression of ErbB2 and EMP3 is the most important indicator of progression-free (P = 0.018 log-rank test) and metastasis-free survival (P = 0.04; log-rank test) for patients with UUT-UC. EMP3 is an important prognostic indicator in the selection of patients with UUT-UC for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2-based cancer therapy.
    The Journal of urology 12/2013; · 3.75 Impact Factor
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    ABSTRACT: Upper urinary tract urothelial carcinoma is a relatively uncommon disease and is diagnosed more frequently at advanced stages. The prognosis of these patients mainly has been related to tumor stage and grade. As a result, the definition of prognostic indicators enabling precise patient selection is mandatory for neoadjuvant or adjuvant therapies. The epithelial membrane protein (EMP2) was identified as one of the up-regulated genes by isoflavones. EMP2 overexpression suppressed foci formation, anchorage-independent growth in vitro, and tumorigenicity in severe combined immunodeficiency mice (all P < 0.05). In addition, a cross-talk between EMP2 and integrins αV and β3 was shown in the regulation of cell adhesion and migration. Higher EMP2 expression was associated with a better progression-free survival (P = 0.008) and cancer-related death (P < 0.001). EMP2 was identified as a tumor-suppressor gene in urinary tract urothelial carcinoma and may be an innovative co-targeting candidate for designing integrin-based cancer therapy.
    American Journal Of Pathology 07/2013; · 4.60 Impact Factor
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    ABSTRACT: To investigate the molecular mechanisms of arsenic (As)-associated carcinogenesis, we performed proteomic analysis on E7 immortalized human uroepithelial cells after treatment with As in vitro. Quantitative proteomics was performed using stable isotope dimethyl labeling coupled with two-dimensional liquid chromatography peptide separation and mass spectrometry (MS)/MS analysis. Among 285 proteins, a total of 26 proteins were upregulated (ratio>2.0) and 18 proteins were downregulated (ratio<0.65) by As treatment, which are related to nucleotide binding, lipid metabolism, protein folding, protein biosynthesis, transcription, DNA repair, cell cycle control, and signal transduction. This study reports the potential significance of nucleophosmin (NPM) in the As-related bladder carcinogenesis. NPM was universally expressed in all of uroepithelial cell lines examined, implying that NPM may play a role in human bladder carcinogenesis. Upregulation of NPM tends to be dose- and time-dependent after As treatment. Expression of NPM was associated with cell proliferation, migration and anti-apoptosis. On the contrary, soy isoflavones inhibited the expression of NPM in vitro. The results suggest that NPM may play a role in the As-related bladder carcinogenesis, and soybean-based foods may have potential in the suppression of As/NPM-related tumorigenesis.
    Toxicology and Applied Pharmacology 10/2009; 242(2):126-35. · 3.98 Impact Factor
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    ABSTRACT: Our profiling experiment demonstrated that prohibitin 1 (PHB) was ubiquitously expressed in uroepithelial and urothelial carcinoma cell lines and exhibited a trend toward a positive relationship with tumor progression. The aim of this study was, therefore, to examine the potential role of PHB in multistage bladder carcinogenesis and predicting patient outcome. Immunohistochemical staining showed that PHB was overexpressed in 141 out of 167 cases (84.4%) of bladder cancer. This expression was positively related to met receptor overexpression (p = 0.04) and to multiple tumors (p = 0.05). Independent factors in predicting patient survival were multiple tumors (p = 0.002), muscle invasion (p = 0.003), and met overexpression (p = 0.05) in a multivariate analysis. Interestingly, patients with superficial bladder cancer overexpressing both PHB and met had a significantly lower recurrence-free survival rate than those not expressing PHB (p = 0.04). Taken together, our findings showed that PHB was activated at an early stage of carcinogenesis and that it may play a synergistic role with met in the progression of human bladder cancer. In addition, we demonstrated that genistein and justicidin A, natural chemoprevention agents, could suppress the expression of PHB in vitro. Thus, targeting PHB would be a useful approach for treating and preventing human bladder cancer.
    Anticancer research 01/2007; 27(2):895-900. · 1.71 Impact Factor