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PLoS One. 2014 Jul 31;9(7):e103882. doi: 10.1371/journal.pone.0103882. eCollection 2014.

Activating transcription factor 4 promotes esophageal squamous cell carcinoma invasion and metastasis in mice and is associated with poor prognosis in human patients.

Author information

1
Department of Gastroenterology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.
2
Department of Oncology, Fuzhou General Hospital of the Nanjing Military Command of the PLA, Fuzhou, China.
3
Department of Oncology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.
4
Department of Gerontology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.

Abstract

BACKGROUND:

Activating transcription factor 4 (ATF4) is a stress response gene that is involved in homeostasis and cellular protection. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remains unknown. In this study, we aimed to determine the clinicopathologic significance of ATF4 in ESCC and its potential role in ESCC invasion and metastasis.

METHODOLOGY/PRINCIPAL FINDINGS:

We demonstrated that ATF4 overexpression is correlated with multiple malignant characteristics and indicates poor prognosis in ESCC patients. ATF4 expression was an independent factor that affected the overall survival of patients with ESCC after surgical resection. ATF4 promoted cell invasion and metastasis by promoting matrix metalloproteinase (MMP)-2 and MMP-7 expression, while its silencing significantly attenuated these activities both in vitro and in vivo.

CONCLUSIONS/SIGNIFICANCE:

We report that ATF4 is a potential biomarker for ESCC prognosis and that its dysregulation may play a key role in the regulation of invasion and metastasis in ESCC cells. The targeting of ATF4 may provide a new strategy for blocking ESCC metastasis.

PMID:
25078779
PMCID:
PMC4117569
DOI:
10.1371/journal.pone.0103882
[Indexed for MEDLINE]
Free PMC Article
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