Data from Characterization of a Candidate Tumor Suppressor Gene Uroplakin 1A in Esophageal Squamous Cell Carcinoma

Abstract

<div>Abstract<p>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 (<i>UPK1A</i>) as a candidate tumor suppressor gene (TSG), and we investigated its function and mechanism in ESCC cells. <i>UPK1A</i> downregulation occurred in 68% of primary ESCCs examined, where it was correlated significantly with promoter hypermethylation (<i>P</i> < 0.05). Ectopic expression of <i>UPK1A</i> 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, <i>c-jun, c-myc</i>, and matrix metalloproteinase 7 (<i>MMP7</i>). Cell cycle arrest elicited by <i>UPK1A</i> at the G<sub>1</sub>-S checkpoint was associated with downregulation of cyclin D1 and cyclin-dependent kinase 4, whereas metastasis suppression was associated with reduction of <i>MMP7</i>. These findings were consistent with evidence derived from clinical samples, where <i>UPK1A</i> downregulation was correlated with lymph node metastasis (<i>P</i> = 0.009), stage (<i>P</i> = 0.015), and overall survival (<i>P</i> < 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. Cancer Res; 70(21); 8832–41. ©2010 AACR.</p></div>