کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8308617 1538497 2018 28 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of DNMT suppresses the stemness of colorectal cancer cells through down-regulating Wnt signaling pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Inhibition of DNMT suppresses the stemness of colorectal cancer cells through down-regulating Wnt signaling pathway
چکیده انگلیسی
Cancer stem cell (CSC) theory reveals a new insight into the understanding of tumorigenesis and metastasis. Recently, DNA methylation is suggested to be a potential epigenetic mechanism for maintenance of CSCs. What's more, studies have shown that DNA methyltransferase (DNMT) is essential for CSCs and deletion of DNMT can reduce tumorigenesis by limiting CSC pool. Therefore, targeting the epigenetic modifiers especially DNA methylation offers an optional strategy for treating human cancers. In the present study we found that DNMT inhibitor 5-Aza-2′-deoxycytidine (5-AzaDC) markedly reduced colorectal CSC abundance in vitro and suppressed liver metastatic tumor growth in vivo. And 5-AzaDC inhibited the expression of active β-catenin and down-regulated the Wnt signaling pathway. The Wnt inhibitors were frequently inactivated by promoter methylation in colorectal cancer; however analysis of TCGA data base showed that only the expression of SFRP1 was significantly reduced in tumors compared to normal tissues. In addition, restoring of SFRP1 expression inhibited the stem cell-like potential of colorectal cancer cells. Our results indicated that inhibition of DNMT blocked the self-renewal of colorectal CSCs and SFRP1 was essential for the maintenance of colorectal CSCs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 47, July 2018, Pages 79-87
نویسندگان
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