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Rab25 is a tumor suppressor gene with anti-angiogenic and anti-invasive activities in esophageal squamous cell carcinoma

icecream 添加于 2012-11-3 13:29 | 1090 次阅读 | 0 个评论

作者
Tong M, Chan KW, Bao JY, Wong K-Y, Chen J-N, Kwan PS, Tang KH, Fu L, Qin Y-R, Lok S, Guan X-Y, Ma S
摘要
Esophageal squamous cell carcinoma (ESCC), the major histologic subtype of esophageal cancer, is a devastating disease characterized by distinctly high incidences and mortality rates. However, there remains limited understanding of molecular events leading to development and progression of the disease, which are of paramount importance to defining biomarkers for diagnosis, prognosis and personalized treatment. By high-throughout transcriptome sequence profiling of non-tumor and ESCC clinical samples, we identified a subset of significantly differentially expressed genes involved in integrin signaling. The Rab25 gene implicated in endocytic recycling of integrins was the only gene in this group significantly downregulated and its downregulation was confirmed as a frequent event in a second larger cohort of ESCC tumor specimens by qPCR and immunohistochemical analyses. Reduced expression of Rab25 correlated with decreased overall survival and was also documented in ESCC cell lines compared to pooled normal tissues. Demethylation treatment and bisulfite genomic sequencing analyses revealed that downregulation of Rab25 expression in both ESCC cell lines and clinical samples was associated with promoter hypermethylation. Functional studies using lentiviral-based overexpression and suppression systems lent direct support of Rab25 to function as an important tumor suppressor with both anti-invasive and anti-angiogenic abilities, through a deregulated FAK-Raf-MEK1/2-ERK signaling pathway. Further characterization of Rab25 may provide a prognostic biomarker for ESCC outcome prediction and a novel therapeutic target in ESCC treatment.
详细资料
- 文献种类: Journal Article
- 期刊名称: Cancer Research
- 期刊缩写: Cancer Res
- 期卷页: 2012年
- 地址: Pathology, The University of Hong Kong
- ISBN: 0008-5472
学科领域生物医药 » 预防卫生学
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