WNT5A antagonizes WNT/beta-catenin signaling and is frequently silenced by promoter CpG methylation in esophageal squamous cell carcinoma
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摘要WNT5A is classified as a non-transforming WNT family member whose role in carcinogenesis is still ambiguous. It exhibits tumor suppressor activities in some cancers (thyroid, brain, breast and colorectum), but is aberrantly upregulated in cancers of lung, stomach and prostate. We investigated its epigenetic alterations and functions in esophageal squamous cell carcinoma (ESCC). With semi-quantitative reverse transcription PC R, we found that WNT5A was silenced or downregulated in 5 of 18 ESCC cell lines, but expressed in normal esophagus tissue and immortalized normal esophageal epithelial cell lines. Promoter CpG methylation of WNT5A was detected in 4 of the 5 downregulated ESCC cell lines, while 5-aza-2'-deoxycytidine treatment induced WNT5A expression and demethylated its promoter in silenced cell lines. WNT5A promoter methylation was frequently detected in primary ESCC (24/36, 67%), but less frequently and weakly in paired surgical marginal esophageal tissues (8/36, 22%; p < 0.01), while no methylation was detected in seven normal esophageal epithelial tissues from healthy donors. Ectopic expression of WNT5A resulted in significant inhibition of clonogenicity and motility of ESC cells, accompanied by a dramatic decrease of intracellular beta-catenin protein level and beta-catenin transcriptional activity. In summary, we show that WNT5A is frequently silenced in ESCC by promoter methylation and exhibits tumor suppressor properties through antagonizing the WNT/beta-catenin pathway. The epigenetic disruption of WNT5A would thus contribute directly to the aberrant activation of WNT/beta-catenin signaling during ESCC pathogenesis.
著者Li JS, Ying JM, Fan YC, Wu LT, Ying Y, Chan ATC, Srivastava G, Tao QA
期刊名稱Cancer Biology and Therapy
出版年份2010
月份9
日期15
卷號10
期次6
出版社LANDES BIOSCIENCE
頁次617 - 624
國際標準期刊號1538-4047
電子國際標準期刊號1555-8576
語言英式英語
關鍵詞esophageal squamous cell carcinoma; methylation; tumor suppressor gene; WNT signaling; WNT5A
Web of Science 學科類別Oncology; ONCOLOGY

上次更新時間 2020-15-09 於 00:41