SOX10, a novel HMG-box-containing tumor suppressor, inhibits growth and metastasis of digestive cancers by suppressing the Wnt/beta-catenin pathway
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摘要SOX10 was identified as a methylated gene in our previous cancer methylome study. Here we further analyzed its epigenetic inactivation, biological functions and related cell signaling in digestive cancers (colorectal, gastric and esophageal cancers) in detail. SOX10 expression was decreased in multiple digestive cancer cell lines as well as primary tumors due to its promoter methylation. Pharmacologic or genetic demethylation reversed SOX10 silencing. Ectopic expression of SOX10 in SOX10-deficient cancer cells inhibits their proliferation, tumorigenicity, and metastatic potentials in vitro and in vivo. SOX10 also suppressed the epithelial to mesenchymal transition (EMT) and stemness properties of digestive tumor cells. Mechanistically, SOX10 competes with TCF4 to bind beta-catenin and transrepresses its downstream target genes via its own DNA-binding property. SOX10 mutations that disrupt the SOX10-beta-catenin interaction partially prevented tumor suppression. SOX10 is thus a commonly inactivated tumor suppressor that antagonizes Wnt/beta-catenin signaling in cancer cells from different digestive tissues.
著者Tong X, Li LL, Li XY, Heng L, Zhong L, Su XW, Rong R, Hu S, Liu WJ, Jia BQ, Liu X, Kou G, Han J, Guo SJ, Hu Y, Li C, Tao Q, Guo YJ
期刊名稱Oncotarget
出版年份2014
月份11
日期15
卷號5
期次21
出版社IMPACT JOURNALS LLC
頁次10571 - 10583
國際標準期刊號1949-2553
語言英式英語
關鍵詞beta-catenin signaling; digestive cancer; methylation; SOX10; tumor suppressor gene
Web of Science 學科類別Cell Biology; Oncology

上次更新時間 2020-23-11 於 00:18