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Elevated serine protease HtrA1 inhibits cell proliferation, reduces invasion, and induces apoptosis in esophageal squamous cell carcinoma by blocking the nuclear factor-kappaB signaling pathway

icecream 添加于 2012-11-3 10:57 | 1122 次阅读 | 0 个评论

作者
Xia J, Wang F, Wang L, Fan Q
摘要
Emerging evidence has demonstrated that high-temperature requirement protein A1 (HtrA1) appears to be involved in several important biological processes in mammals such as growth, apoptosis, embryogenesis, invasion, metastasis, and cancer and has been verified to be reduced in a variety of human tumors. However, its precise functions and molecular mechanisms in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we detected HtrA1 level in ESCC tissues and cells and investigated the biological roles of HtrA1 in ESCC. We found that expressions of HtrA1 mRNA and protein in ESCC tissues and cells were significantly lower than those in normal esophageal epithelial tissues and cells (P < 0.05). Expressions of HtrA1 mRNA and protein were closely associated with TNM staging and lymph node metastasis (P < 0.05). Additionally, the survival rate of patients with low HtrA1 level was lower than those patients with high HtrA1 level (P < 0.05). Elevated HtrA1 level markedly inhibited cell proliferation in vitro and in vivo, reduced cell invasion in vitro, and induced cell apoptosis. Notably, HtrA1 overexpression inhibited phosphorylation levels of IkappaBalpha and p65 subunit of the NF-kappaB signaling pathway, but increased total IkappaBalpha level, coupled with decreases of Ki-67, Bcl-2, Bcl-xL, cyclin D1, and MMP-9 proteins and increase of caspase-3 activity. Overall, these data suggest that HtrA1 may play critical roles in the tumorgenesis and progression of ESCC, and HtrA1 overexpression exerts its anti-tumor effect by blocking the NF-kappaB signaling pathway; thus, manipulation of HtrA1 may be an effective molecular target for ESCC treatment.
详细资料
- 文献种类: Journal Article
- 期刊名称: Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
- 期刊缩写: Tumour Biol
- 期卷页: 2012年
- 地址: Department of Oncology, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan, 450052, People's Republic of China
- ISBN: 1010-4283
学科领域生物医药 » 预防卫生学
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