• Curr Pharm Biotechnol · Feb 2011

    Review

    Network of WNT and other regulatory signaling cascades in pluripotent stem cells and cancer stem cells.

    • Masaru Katoh.
    • Genetics and Cell Biology Section, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan. mkatoh-kkr@umin.ac.jp
    • Curr Pharm Biotechnol. 2011 Feb 1;12(2):160-70.

    AbstractCanonical WNT signaling activation leads to transcriptional up-regulation of FGF ligand, Notch ligand, non-canonical WNT ligand, WNT antagonist, TGFβ antagonist, and MYC. Non-canonical WNT signals inhibit canonical WNT signaling by using MAP3K7-NLK signaling cascade. Hedgehog up-regulates Notch ligand, WNT antagonist, BMP antagonists, and MYCN. TGFβ up-regulates non-canonical WNT ligand, CDK inhibitors, and NANOG, while BMP up-regulates Hedgehog ligand. Based on these mutual regulations, WNT, FGF, Notch, Hedgehog, and TGFβ/BMP signaling cascades constitute the stem-cell signaling network, which plays a key role in the maintenance or homeostasis of pluripotent stem cells and cancer stem cells. Human embryonic stem cells (ESCs) are supported by FGF and TGFβ/Nodal/Activin signals, whereas mouse ESCs by LIF and canonical WNT signals. Combination of TGFβ inhibitor and canonical WNT activator alter the character of human induced pluripotent stem cells (iPSCs) from human ESC-like to mouse ESC-like. Fine-tuning of WNT, FGF, Notch, TGFβ/BMP, and Hedgehog signaling network by using small-molecule compounds could open the door for regenerative medicine utilizing pluripotent stem cells without tumorigenic potential. Because FGF, Hedgehog, TGFβ, and non-canonical WNT signals synergistically induce EMT regulators, such as Snail (SNAI1), Slug (SNAI2), TWIST, and ZEB2 (SIP1), tumor-stromal interaction at the invasion front aids cancer stem cells to acquire more malignant phenotype. Cancer stem cells occur as mimetics of normal tissue stem cells based on germ-line variation, epigenetic change, and somatic mutation of stem-cell signaling components, and then acquire more malignant phenotype based on accumulation of additional epigenetic and genetic alterations, and tumor-stromal interaction at the invasion front.

      Pubmed     Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…