FOXM1 regulated by ERK pathway mediates TGF-ß1-induced EMT in NSCLC.
Oncol Res
; 22(1): 29-37, 2014.
Article
en En
| MEDLINE
| ID: mdl-25700356
ABSTRACT
FOXM1, a member of the Forkhead transcriptional family, plays an important role in the EMT process, and transforming growth factor-ß1 (TGF-ß1) has been identified as the most potent factor that can independently induce EMT in various types of cancer cells. Here we examine the important role of FOXM1 in TGF-ß1-induced EMT and investigate the mechanism underlying the relationship between TGF-ß1 and FOXM1. Lentivirus-mediated transfection was used to stably upregulate the expression of FOXM1, and a small interfering RNA (siRNA) was introduced to silence the expression of FOXM1. Transwell and wound-healing assays were then performed to assess the invasion and motility potential of non-small cell lung cancer (NSCLC) cells. The NSCLC cell lines exhibited EMT characteristics, including an elongated fibroblastoid shape, induced expression of EMT marker proteins, and increased migratory and invasive potential after induction with TGF-ß1. The overexpression of FOXM1 enhanced TGF-ß1-induced EMT in NSCLC cells. Knockdown of FOXM1 reversed TGF-ß1-induced EMT in NSCLC cell lines but had no effect on the phosphorylation level of ERK. Additionally, U0126, an ERK signaling inhibitor, exerted a reversible effect on TGF-ß1-induced EMT and inhibited FOXM1 expression. FOXM1 regulated by the ERK pathway can mediate TGF-ß1-induced EMT in NSCLC and is a potential target for the treatment of NSCLC.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
/
Factores de Transcripción Forkhead
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Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article