Details

Autor(en) / Beteiligte

• Fang, Wang-Kai
• Liao, Lian-Di
• Gu, Wei
• Chen, Bo
• Wu, Zhi-Yong
• Wu, Jian-Yi
• Shen, Jian
• Xu, Li-Yan
• Li, En-Min

Titel

Down-regulated γ-catenin expression is associated with tumor aggressiveness in esophageal cancer

Ist Teil von

• World journal of gastroenterology : WJG, 2014-05, Vol.20 (19), p.5839-5848

Ort / Verlag

United States: Baishideng Publishing Group Inc

Erscheinungsjahr

2014

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• AIM:To evaluate the significance ofγ-catenin in clinical pathology,cellular function and signaling mechanism in esophageal squamous cell carcinoma(ESCC).METHODS:The mRNA expression ofγ-catenin was detected by real-time quantitative reverse transcription-polymerase chain reaction in 95 tissue specimens and evaluated for association with the clinicopathologic characteristics and survival time of patients with ESCC.siRNAs against humanγ-catenin were used to inhibitγ-catenin expression.Hanging drop aggregation assay and dispase-based dissociation assay were performed to detect the effect ofγ-catenin on ESCC cell-cell adhesion.Transwell assay was performed to determine cell migration.Luciferase-based transcriptional reporter assay(TOPflash)was used to measureβ-catenindependent transcription in cells with reducedγ-catenin expression.The expression and subcellular localizations ofβ-catenin and E-cadherin were examined using Western blot and immunofluorescence analysis.RESULTS:γ-catenin mRNA expression was significantly associated with tumor histological grade(P=0.017)in ESCC.Kaplan-Meier survival analysis showed thatγ-catenin expression levels had an impact on the survival curve,with lowγ-catenin indicating worse survival(P=0.003).The multivariate Cox regression analysis demonstrated thatγ-catenin was an independent prognostic factor for survival.Experimentally,silencingγ-catenin caused defects in cell-cell adhesion and a concomitant increase in cell migration in both KYSE150 and TE3 ESCC cells.Analysis of Wnt signaling revealed no activation event associated withγ-catenin expression.Totalβ-catenin and Triton X-100-insolubleβ-catenin were significantly reduced in theγ-catenin-specific siRNA-transfected KYSE150 and TE3 cells,whereas Triton X-100-solubleβ-catenin was not altered.Moreover,knocking downγ-catenin expression resulted in a significant decrease of E-cadherin and Triton X-100-insoluble desmocollin-2,along with reducedβ-catenin and E-cadherin membrane localization in ESCC cells.CONCLUSION:γ-catenin is a tumor suppressor in ESCC and may serve as a prognostic marker.Dysregulated expression ofγ-catenin may play important roles in ESCC progression.