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Inhibition of DNMT suppresses the stemness of colorectal cancer cells through down-regulating Wnt signaling pathway.

Author information

Affiliations

  • 1. Department of Pharmacy, Changhai Hospital, The Second Military Medical University, Shanghai, China.
      Authors
    • Li S 1
    • Zhao N 1
    • Zhu B 1
    • Zhang L 1
    (4 authors)
  • 2. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
      Authors
    • Han Z 2
    • Yang X 2
    • Sheng D 2
    • Wei L 2
    (4 authors)
  • 3. Department of Pharmacology, Fudan University School of Pharmacy, Shanghai, China.
      Authors
    • Zhang Q 3
    (1 author)
  • 4. Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
      Authors
    • Hou J 4
    (1 author)
  • 5. Third Department of General Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
      Authors
    • Guo S 5
    (1 author)

ORCIDs linked to this article

Cellular Signalling, 27 Mar 2018, 47:79-87
https://doi.org/10.1016/j.cellsig.2018.03.014 PMID: 29601907 

Abstract 

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.

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Read article at publisher's site: https://doi.org/10.1016/j.cellsig.2018.03.014

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Funding 

Funders who supported this work.

Health Bureau Foundation of Shanghai (1)

National Natural Science Foundation of China (3)

Postdoctoral Science Foundation of China (1)