RESUMEN
The brain expressed xlinked gene 1 (BEX1) is a member of the BEX family and is aberrantly expressed in many cancers. However, the clinical significance of BEX1 expression level and its role in the pathology of esophageal squamous cell cancer (ESCC) remain unknown. In the present study, we determined BEX1 expression in the tumor and adjacent normal tissues from 118 ESCC patients by immunohistochemistry and determined the proliferation and growth of ESCC cells following ectopic overexpression of BEX1 in cultured cells and in mouseESCC xenografts. We observed that BEX1 was downregulated in ESCC tissues compared to adjacent normal tissues, and low BEX1 expression was significantly associated with larger ESCC tumor volume (P<0.001), advanced T stage (P=0.011) and advanced clinical stage (P=0.039). Additionally, survival analysis revealed that low expression of BEX1 significantly predicted poor prognosis in patients with ESCC (P<0.001). Multivariate analysis revealed that low BEX1 expression was an independent prognostic factor of poor survival (P=0.039). In vitro analysis revealed that overexpression of BEX1 inhibited ESCC cell proliferation and colony formation. Furthermore, in vivo tumorigenesis assays revealed that ectopic overexpression of BEX1 suppressed ESCC tumor growth in mice. Further immunoblotting analysis demonstrated that BEX1 upregulation led to reduced expression and phosphorylation of NFκB p65, indicating inhibition of the NFκB signaling pathway by BEX1. Our findings indicated that low BEX1 expression may be an independent prognostic marker for poor survival and may serve as a potential target for ESCC therapy.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Proteínas del Tejido Nervioso/metabolismo , Animales , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Esófago/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Fosforilación , Pronóstico , Análisis de Supervivencia , Factor de Transcripción ReIA/metabolismo , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Hepatocyte cell adhesion molecule (hepaCAM), a new type of CAM, belongs to the immunoglobulin superfamily. Recently, hepaCAM was reported to be implicated in cancer development, and many researchers investigated its biological function in the tumorigenesis of various cancers. However, what kind of role hepaCAM plays in colorectal cancer (CRC) remains unknown. In this study, we found that hepaCAM was downregulated in CRC tissues and cell lines. Overexpression of hepaCAM inhibited CRC cell proliferation, migration, and invasion in vitro. Furthermore, the tumorigenesis assay showed that increased expression of hepaCAM suppressed CRC tumor growth and metastasis in vivo. We also demonstrated that overexpression of hepaCAM reduced the protein expression levels of ß-catenin, cyclin D1, and c-Myc, indicating its inhibitory effect on the Wnt/ß-catenin signaling pathway. In conclusion, our study results suggest hepaCAM as a promising therapeutic target for CRC and provide a better understanding for the molecular basis of CRC progression.
