RESUMEN

Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters. CTHRC1 promotes cervical cancer cell migration and invasion in vitro and metastasis in vivo. E6/E7 regulates the expression of CTHRC1 in cervical cancer by E6/E7-p53-POU2F1 (POU class 2 homeobox 1) axis. Futhermore, CTHRC1 activates Wnt/PCP signaling pathway. Take together, E6/E7-p53-POU2F1-CTHRC1 axis promotes cervical cancer cell invasion and metastasis and may act as a potential therapeutic target for interventions against cervical cancer invasion and metastasis.

Asunto(s)

Polaridad Celular , Proteínas de la Matriz Extracelular/metabolismo , Factor 1 de Transcripción de Unión a Octámeros/metabolismo , Proteínas Oncogénicas Virales/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Vía de Señalización Wnt , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas de la Matriz Extracelular/sangre , Proteínas de la Matriz Extracelular/genética , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Curva ROC , Regulación hacia Arriba/genética , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/genética