S100A6 promotes cell proliferation in human nasopharyngeal carcinoma via the p38/MAPK signaling pathway.
Mol Carcinog
; 56(3): 972-984, 2017 03.
Article
en En
| MEDLINE
| ID: mdl-27596819
ABSTRACT
An elevated level of S100A6 is associated with poor outcomes of many tumor types, but, how S100A6 contributes to nasopharyngeal carcinoma (NPC) progression remains unknown. Here, we investigated the expression and prognostic significance of S100A6 in NPC and explored the molecular mechanisms under-lying the role of S100A6 in NPC development. The results showed that S100A6 was markedly up-regulated in NPC tissues and cell lines compared to paired peritumoral normal tissues and a normal nasopharyngeal epithelial cell line, respectively. In tissues from 92 NPC patients, high S100A6 expression was associated with advanced N stage, locoregional failure and disease progression and was predictive of poor locoregional recurrence-free survival (LRRFS, P = 0.001) and progression-free survival (PFS, P = 0.001). Multivariate analysis showed that S100A6 is an independent prognostic factor for LRRFS and PFS. Silencing S100A6 using siRNA or shRNA significantly suppressed NPC cell proliferation, colony formation and p38/mitogen-activated protein kinase (MAPK) activity in vitro and inhibited tumor growth in a xenograft mouse model of NPC. In contrast, overexpressing S100A6 via plasmid transfection resulted in increased NPC cell proliferation and p38/MAPK activation. S100A6-induced proliferation was abolished by a p38 inhibitor. In summary, S100A6 may be a new prognostic marker of NPC and may promote NPC development via the activation of p38/MAPK signaling pathways. These findings suggest S100A6/p38/MAPK signaling as a potential therapeutic target for NPC. © 2016 Wiley Periodicals, Inc.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Carcinoma
/
Proteínas S100
/
Regulación hacia Arriba
/
Neoplasias Nasofaríngeas
/
Proteínas de Ciclo Celular
/
Sistema de Señalización de MAP Quinasas
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Mol Carcinog
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
China