Protein Expression Patterns of Ezrin Are Predictors of Progression in T1G3 Bladder Tumours Treated with Nonmaintenance Bacillus Calmette-Guérin

Palou, Joan; Algaba, Ferrán; Vera, Irene; Rodríguez, Ó.; Villavicencio, H.; Sänchez‐Carbayo, Marta

doi:10.1016/j.eururo.2008.09.062

Cited by 57 publications

(44 citation statements)

References 29 publications

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“…In our series, the loss of KiSS-1 expression was observed in those metastatic patients that displayed cytoplasmic Filamin A expression (54). Importantly, this report revealed the regulation of the expression of these proteins by KiSS-1 (54,55). This observation may indicate a cooperative involvement of KiSS-1 together with Ezrin and Filamin A, among others, in the suppression of metastatic potential of bladder tumors.…”

Section: Discussionmentioning

confidence: 76%

Differential Protein Expression Profiling by iTRAQ-Two-dimensional LC-MS/MS of Human Bladder Cancer EJ138 Cells Transfected with the Metastasis Suppressor KiSS-1 Gene

Ruppen

Grau

Orenes‐Piñero

et al. 2010

Molecular & Cellular Proteomics

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KiSS-1 is a metastasis suppressor gene reported to be involved in the progression of several solid neoplasias. The loss of KiSS-1 gene expression has been shown to be inversely correlated with increasing tumor stage, distant metastases, and poor overall survival in bladder tumors. To identify the molecular pathways associated with the metastasis suppressor role of KiSS-1 in bladder cancer, we carried out a proteomics analysis of bladder cancer cells (EJ138) transiently transfected with a vector encompassing the full-length KiSS-1 gene using an iTRAQ (isobaric tags for relative and absolute quantitation) approach. Protein extracts collected after 24-and 48-h transfection were fractionated and cleaved with trypsin, and the resulting peptides were labeled with iTRAQ reagents. The Bladder cancer represents the fourth most common malignancy among men and the eighth cause of male cancer deaths (1). Bladder cancer can be classified based on the depth of invasion. Clinically, ϳ75% of transitional cell carcinomas (TCCs) 1 are non-muscle-invasive (pTis, pTa, and pT1), 20% are muscle infiltrating (pT2-pT4), and 5% are metastatic at the time of diagnosis (1). Low grade tumors are always papillary and usually non-invasive, whereas high grade tumors can be either papillary or non-papillary and are often invasive. Patients diagnosed with localized TCC have a 5-year relative survival rate over 90%. However, patients presenting with regional and distant metastatic disease spread have 5-year relative survival rates of lower than 50 and 10%, respectively (1). Bladder cancer progression and the development of secondary metastases follow complex sequential steps. The changes at the genetic and/or epigenetic level to the many genes involved in critical cell functions are not completely understood (2).KiSS-1 has been shown to suppress metastases without affecting tumorigenicity in melanoma and breast cancer cells (3-7). It maps to chromosome 1q32 (8) and is regulated by genes mapping to chromosome 6 (3-7). KiSS-1 encodes a 145-amino acid protein, which is processed into kisspeptins of several sizes (9 -11). Kisspeptins have been shown to control the onset of puberty and inhibit cancer metastasis of different tumor types (9 -11). Experimental and clinical studies indicate KiSS-1 to be a functionally active metastasis suppressor gene in several solid tumors (12-19). Molecular profiling analysis revealed that KiSS-1 was lost in advanced cell 1 The abbreviations used are: TCC, transitional cell carcinoma; EF, error factor; FDR, false discovery rate; iTRAQ, isobaric tags for relative and absolute quantitation; RB, retinoblastoma; TP53, tumor protein 53; CI, confidence interval; EV, empty vector; Ct, cycle threshold. Research

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Section: Discussionmentioning

confidence: 76%

Differential Protein Expression Profiling by iTRAQ-Two-dimensional LC-MS/MS of Human Bladder Cancer EJ138 Cells Transfected with the Metastasis Suppressor KiSS-1 Gene

Ruppen

Grau

Orenes‐Piñero

et al. 2010

Molecular & Cellular Proteomics

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“…Interesting results were achieved with cell proliferative factors p53 and Ki-67 overexpression [5][6][7][8][9] , but other studies seem to indicate that these molecules are not suitable for predicting BCG treatment response [10][11][12][13][14][15] . Markers such as heat shock protein (HSP)-90 and anti-HSP-65 antibodies have also shown a certain relative correlation with BCG outcome [16][17][18][19] .…”

mentioning

confidence: 99%

IL-4 and TNF-α Polymorphisms Are Associated with Risk of Multiple Superficial Tumors or Carcinoma in situ Development

Lima

Silva

Amaro³

et al. 2011

Urol Int

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Introduction: This study evaluates the influence of clinicopathological characteristics, bacillus Calmette-Guérin (BCG) therapeutic schedule [maintenance (mBCG) or induction (iBCG)], and TNF-α and IL-4 polymorphisms on the outcome of non-muscle-invasive bladder cancer patients treated with BCG. Material and Methods: DNA was extracted from 125 bladder cancer patients treated with BCG; TNF-308G/A and IL4-590C/T polymorphisms were genotyped. Results: The TNF-308A allele carriers had an increased risk of developing multiple tumors (OR: 2.80, p = 0.031). However, IL4-590 T carriers also had an increased risk of developing multiple and carcinoma in situ tumors (OR: 2.52, p = 0.033). For these polymorphisms, no association was found with BCG treatment outcome. When treated with iBCG, patients with multiple tumors had shorter recurrence-free survival (RFS) compared with those with a single tumor (p = 0.004); nevertheless, patients with multifocal tumors have improved RFS when treated with mBCG. Conclusions: Overall, the results suggest that multiple tumors and/or carcinoma in situ development are associated with the IL4-590C/T and TNF-308G/A polymorphisms, and emphasize the effectiveness of the mBCG schedule.

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“…It may also contribute to the formation of the scaffolding between the actin cytoskeleton and receptor retention (6) as well as filopodia formation (1). Ezrin is overly expressed in various cancers and associated with cancer metastasis (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

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confidence: 99%

Berberine Inhibits Metastasis of Nasopharyngeal Carcinoma 5-8F Cells by Targeting Rho Kinase-mediated Ezrin Phosphorylation at Threonine 567

Tang

Wang

Duan

et al. 2009

Journal of Biological Chemistry

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Ezrin is highly expressed in metastatic tumors and is involved in filopodia formation as well as promotion of tumor metastasis. Thus, Ezrin may serve as a potential target for anti-metastatic therapy. This study demonstrates that berberine reduces filopodia formation of a nasopharyngeal carcinoma (NPC) cell line, 5-8F, at non-cytotoxic concentrations. Furthermore, invasion and motility of 5-8F cells are decreased in a dose-and time-dependent manner, resulting in 73.0% invasion and 67.0% motility inhibition at 20 M. The inhibitory effects of berberine on 5-8F cell metastasis were further confirmed in a mouse model of metastasis. Berberine treatment in vivo resulted in a 51.1% inhibition of tumor metastasis to the lymph nodes and decreased Ezrin phosphorylation at threonine 567 in metastatic samples. Berberine suppressed the presence of phosphorylated Ezrin (phospho-Ezrin) in a dose-and time-dependent manner but had no effect on total Ezrin protein expression at non-cytotoxic concentrations. Furthermore, the inhibitory effects of berberine on phospho-Ezrin were dependent on the suppression of Rho kinase activity. Reduction of Ezrin phosphorylation at Thr 567 by berberine was associated with its inhibitory effect on filopodia formation in 5-8F cells. However, berberine did not effectively inhibit the motility and invasion of NPC cells containing Ezrin Thr 567 mutants. These results confirm that berberine inhibits Ezrin phosphorylation at Thr 567 . Nonetheless, berberine reduces motility and invasion of cells and inhibits tumor metastasis. The reduction of Rho kinase-mediated Ezrin phosphorylation mediated by berberine may be a novel anti-metastatic pathway in NPC 5-8F cells.

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Protein Expression Patterns of Ezrin Are Predictors of Progression in T1G3 Bladder Tumours Treated with Nonmaintenance Bacillus Calmette-Guérin

Cited by 57 publications

References 29 publications

Differential Protein Expression Profiling by iTRAQ-Two-dimensional LC-MS/MS of Human Bladder Cancer EJ138 Cells Transfected with the Metastasis Suppressor KiSS-1 Gene

Differential Protein Expression Profiling by iTRAQ-Two-dimensional LC-MS/MS of Human Bladder Cancer EJ138 Cells Transfected with the Metastasis Suppressor KiSS-1 Gene

IL-4 and TNF-α Polymorphisms Are Associated with Risk of Multiple Superficial Tumors or Carcinoma in situ Development

Berberine Inhibits Metastasis of Nasopharyngeal Carcinoma 5-8F Cells by Targeting Rho Kinase-mediated Ezrin Phosphorylation at Threonine 567

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