RESUMEN

Pyruvate kinase M2 (PKM2) mainly catalyzes glycolysis, but it also exerts non-glycolytic functions in several cancers. While it has been shown to interact with the human papillomavirus 16 (HPV16) E7 oncoprotein, the functional significance of PKM2 in HPV-associated cervical cancer has been elusive. Here, we show that HPV16 E7 increased the expression of PKM2 in cervical cancer cells. TCGA data analyses revealed a higher level of PKM2 in HPV+ than HPV- cervical cancers and a worse prognosis for patients with high PKM2 expression. Functionally, we demonstrate that shRNA-mediated PKM2 knockdown decreased the proliferation of HPV+ SiHa cervical cancer cells. PKM2 knockdown also inhibited the E7-induced proliferation of cervical cancer cells. ML265 activating the pyruvate kinase function of PKM2 inhibited cell cycle progression and colony formation. ML265 treatments decreased phosphorylation of PKM2 at the Y105 position that has been associated with non-glycolytic functions. On the contrary, HPV16 E7 increased the PKM2 phosphorylation. Our results indicate that E7 increases PKM2 expression and activates a non-glycolytic function of PKM2 to promote cervical cancer cell proliferation.

Asunto(s)

Proteínas Portadoras/genética , Proliferación Celular/genética , Papillomavirus Humano 16/patogenicidad , Proteínas de la Membrana/genética , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Hormonas Tiroideas/genética , Neoplasias del Cuello Uterino/virología , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Proliferación Celular/fisiología , Femenino , Expresión Génica , Papillomavirus Humano 16/metabolismo , Humanos , Proteínas de la Membrana/metabolismo , Proteínas Oncogénicas Virales/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Fosforilación , Hormonas Tiroideas/metabolismo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Proteínas de Unión a Hormona Tiroide