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Stathmin 1 (STMN1) is a microtubule-regulated protein that plays an important role in tumour cell proliferation and migration. Overexpression of STMN1 is associated with clinicopathological characteristics in many human cancers. The aim of the present study was to investigate STMN1 expression, its correlation with clinicopathological characteristics, and its exact biological function in oesophageal squamous cell carcinoma (ESCC). STMN1 levels were measured in the ESCC tissue specimens of 276 patients by immunohistochemistry (IHC) to assess the prognostic efficacy of STMN1. IHC showed that patients with overexpression of STMN1 had a poorer prognosis compared with those with low expression, both in regards to 5-year overall survival (OS; 21.2 vs. 53.7%, P<0.001) and disease-free survival (DFS; 20.6 vs. 50.9%, P<0.001). STMN1 overexpression was associated with lower cell differentiation in tumour grade (correlation coefficient: 0.127, P=0.037). In multivariate analysis, STMN1 expression was found to be an independent prognostic factor for both OS (P<0.001; 95% CI, 1.555-2.970) and DFS (P=0.001; 95% CI, 1.978-2.444). Compared with the control, STMN1 downregulation significantly decreased cell migration, invasion and proliferation, whereas these were increased by STMN1 upregulation. STMN1 expression was significantly associated with prognosis and tumour differentiation in ESCC, indicating that STMN1 expression is an independent prognostic factor for ESCC and could be a potential biomarker. Regulating the expression of STMN1 could influence tumour cell motility, invasion and proliferation.

Aim: To evaluate the significance of γ-catenin in clinical pathology, cellular function and signaling mechanism in esophageal squamous cell carcinoma (ESCC)., Methods: The mRNA expression of γ-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 human γ-catenin were used to inhibit γ-catenin expression. Hanging drop aggregation assay and dispase-based dissociation assay were performed to detect the effect of γ-catenin on ESCC cell-cell adhesion. Transwell assay was performed to determine cell migration. Luciferase-based transcriptional reporter assay (TOPflash) was used to measure β-catenin-dependent transcription in cells with reduced γ-catenin expression. The expression and subcellular localizations of β-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 that γ-catenin expression levels had an impact on the survival curve, with low γ-catenin indicating worse survival (P = 0.003). The multivariate Cox regression analysis demonstrated that γ-catenin was an independent prognostic factor for survival. Experimentally, silencing γ-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 with γ-catenin expression. Total β-catenin and Triton X-100-insoluble β-catenin were significantly reduced in the γ-catenin-specific siRNA-transfected KYSE150 and TE3 cells, whereas Triton X-100-soluble β-catenin was not altered. Moreover, knocking down γ-catenin expression resulted in a significant decrease of E-cadherin and Triton X-100-insoluble desmocollin-2, along with reduced β-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 of γ-catenin may play important roles in ESCC progression.

In animals ranging from fish to mice, the function of DACT2 as a negative regulator of the TGF-β/Nodal signal pathway is conserved in evolution, indicating that it might play an important role in human cancer. In this study, we showed that tumors with higher DACT2 protein level were correlated with better differentiation and better survival rate in patients with esophageal squamous cell carcinoma. Restored expression of DACT2 significantly inhibited growth, migration, and invasion of ESCC cells in vitro, and reduced tumorigenicity in vivo. Furthermore, when DACT2 expression was restored, the activity of TGF-β/SMAD2/3 was suppressed via both proteasome and lysosomal degradation pathways, leading to F-actin rearrangement that might depend on the involvement of cofilin and ezrin-redixin-moesin (ERM) proteins. Taken together, we propose here that DACT2 serves as a prognostic marker that reduces tumor cell malignancy by suppressing TGF-β signaling and promotes actin rearrangement in ESCC.

Aim: To investigate the expression profile of miRNA in esophageal squamous cell carcinoma (ESCC)., Methods: The expression profile of miRNA in ESCC tissues was analyzed by miRNA microarray. The expression levels of miR-143 and miR-145 in 86 ESCC patients were determined by real-time polymerase chain reaction (PCR) using TaqMan assay. The mobility effect was estimated by wound-healing using esophageal carcinoma cells transfected with miRNA expression plasmids., Results: A set of miRNAs was found to be deregulated in the ESCC tissues, and the expression levels of miR-143 and -145 were significantly decreased in most of the ESCC tissues examined. Both miR-143 and miR-145 expression correlated with tumor invasion depth. The transfection of human esophageal carcinoma cells with miR-143 and miR-145 expression plasmids resulted in a greater inhibition of cell mobility, however, the protein level of the previously reported target of miR-145, FSCN1, did not show any significant downregulation., Conclusion: These findings suggest that the deregulation of miRNAs plays an important role in the progression of ESCC. Both miR-143 and miR-145 might act as anti-oncomirs common to ESCC.

The transforming growth factor beta (TGF-beta) signaling pathway plays an important role in growth and development, and is critically involved in the genesis and development of tumors. Syndecan-2 (SDC2) and Cysteine-rich 61 (CYR61) are important genes in this pathway and SDC2 is known to be a significant upstream regulator of TGF-beta signaling. However, the roles of SDC2 and CYR61 in the development of esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study, we investigated the relationship between SDC2 and CYR61 mRNA expression levels and disease prognosis in patients with ESCC. The mRNA expression of SDC2 and CYR61 was detected by quantitative real-time RT-PCR in 77 tissue specimens. Quantitative real-time RT-PCR showed that SDC2 and CYR61 mRNA expression levels were aberrant in ESCC tissue (P<0.01) and that SDC2 mRNA expression was significantly associated with tumor size (P=0.024) in ESCC. CYR61 mRNA expression was significantly associated with regional lymph node metastasis (P=0.034) and tumor size (P=0.03). A positive correlation between SDC2 and CYR61 (r=0.770; P<0.001) mRNA expression was observed. Moreover, we observed significant associations between altered expression of SDC2/CYR61 and regional lymph node metastasis (P=0.009) and TNM stages (P=0.033). Aberrant mRNA expression of CYR61 and SDC2/CYR61 (P=0.005 and P=0.026, respectively) were significantly associated with patient survival time. The multivariate Cox regression analysis showed that SDC2 and CYR61 were independent prognostic factors for survival. Our findings suggest that SDC2 may act as an a upstream regulator of the TGF-beta signaling pathway and regulate the expression of downstream target genes. Moreover, SDC2 and CYR61 expression affect the severity of cancer, and the survival of patients with ESCC. Importantly, we report that SDC2 and CYR61 are significant, independent prognostic factors for survival in ESCC. These findings may have implications for targeted therapies in patients with ESCC.