Characterization of tumor-suppressive function of SOX6 in human esophageal squamous cell carcinoma.

By using cDNA microarray analysis, we identified a transcriptional factor, SOX6, was frequently downregulated in esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the role of SOX6 in human esophageal cancer development, and to examine the prevalence and clinical significance of SOX6 downregulation in ESCC. Expressions of SOX6 mRNA in 50 ESCCs and SOX6 protein in 300 ESCCs were investigated by semiquantitative RT-PCR and immunohistochemistry, respectively. The tumor-suppressive function of SOX6 was characterized by cell growth, foci formation, wound-healing and cell invasive assays, and tumor xenograft experiment. Western blot analysis was applied to detect protein expression levels. SOX6 was frequently downregulated in primary ESCCs in both mRNA level (29/50, 58%) and protein level (149/219, 68.0%), which was significantly associated with the poor differentiation (P = 0.029), lymph node metastases (P = 0.014), advanced TNM stage (P = 0.000), and disease-specific survival (P < 0.001). Multivariate analysis indicated that the downregulation of SOX6 (P = 0.000) was a significant independent prognostic factors for ESCC. Functional studies showed that SOX6 was able to suppress both in vitro and in vivo tumorigenic ability of ESCC cells. The tumor-suppressive mechanism of SOX6 was associated with its role in G1/S cell-cycle arrest by upregulating expressions of p53 and p21(WAF1/CIP1) and downregulating expressions of cyclin D1/CDK4, cyclin A, and β-catenin. We provided the first evidence that SOX6 is a novel tumor-suppressor gene in ESCC development and is a potential prognostic marker in ESCC.

Qin YR ，Tang H ，Xie F ，Liu H ，Zhu Y ，Ai J ，Chen L ，Li Y ，Kwong DL ，Fu L ，Guan XY ... -  《-》

Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma.

Zhu C ，Qin YR ，Xie D ，Chua DT ，Fung JM ，Chen L ，Fu L ，Hu L ，Guan XY ... -  《-》

Characterization of a candidate tumor suppressor gene uroplakin 1A in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is increasing in incidence, but the knowledge of the genetic underpinnings of this disease remains limited. In this study, we identified the tetraspanin cell surface receptor uroplakin 1A (UPK1A) as a candidate tumor suppressor gene (TSG), and we investigated its function and mechanism in ESCC cells. UPK1A downregulation occurred in 68% of primary ESCCs examined, where it was correlated significantly with promoter hypermethylation (P < 0.05). Ectopic expression of UPK1A in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation in nude mice. Mechanistic investigations suggested that these effects may be mediated by inhibiting nuclear translocation of β-catenin and inactivation of its downstream targets, including cyclin-D1, c-jun, c-myc, and matrix metalloproteinase 7 (MMP7). Cell cycle arrest elicited by UPK1A at the G(1)-S checkpoint was associated with downregulation of cyclin D1 and cyclin-dependent kinase 4, whereas metastasis suppression was associated with reduction of MMP7. These findings were consistent with evidence derived from clinical samples, where UPK1A downregulation was correlated with lymph node metastasis (P = 0.009), stage (P = 0.015), and overall survival (P < 0.0001). Indeed, multivariate cyclooxygenase regression analysis showed that UPK1A was an independent prognostic factor for overall survival. Taken together, our findings define a function for UPK1A as an important TSG in ESCC development.

Kong KL ，Kwong DL ，Fu L ，Chan TH ，Chen L ，Liu H ，Li Y ，Zhu YH ，Bi J ，Qin YR ，Law SY ，Guan XY ... -  《-》

Prognostic significance of fascin overexpression in human esophageal squamous cell carcinoma.

Hashimoto Y ，Ito T ，Inoue H ，Okumura T ，Tanaka E ，Tsunoda S ，Higashiyama M ，Watanabe G ，Imamura M ，Shimada Y ... -  《CLINICAL CANCER RESEARCH》

An inducible short-hairpin RNA vector against osteopontin reduces metastatic potential of human esophageal squamous cell carcinoma in vitro and in vivo.

Ito T ，Hashimoto Y ，Tanaka E ，Kan T ，Tsunoda S ，Sato F ，Higashiyama M ，Okumura T ，Shimada Y ... -  《CLINICAL CANCER RESEARCH》