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    Development of an arteriolar niche and self-renewal of breast cancer stem cells by lysophosphatidic acid/protein kinase D signaling

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    Author
    Jiang, Yinan
    Guo, Yichen
    Hao, Jinjin
    Guenter, Rachael
    Lathia, Justin
    Beck, Adam W
    Hattaway, Reagan
    Hurst, Douglas
    Wang, Qiming Jane
    Liu, Yehe
    Cao, Qi
    Krontiras, Helen
    Chen, Herbert
    Silverstein, Roy
    Ren, Bin
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    Date
    2021-06-24
    Journal
    Communications Biology
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1038/s42003-021-02308-6
    Abstract
    Breast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. The regulatory mechanisms of BCSC interactions with the vascular niche within the tumor microenvironment (TME) and their self-renewal are currently under extensive investigation. We have demonstrated the existence of an arteriolar niche in the TME of human BC tissues. Intriguingly, BCSCs tend to be enriched within the arteriolar niche in human estrogen receptor positive (ER+) BC and bi-directionally interact with arteriolar endothelial cells (ECs). Mechanistically, this interaction is driven by the lysophosphatidic acid (LPA)/protein kinase D (PKD-1) signaling pathway, which promotes both arteriolar differentiation of ECs and self-renewal of CSCs likely via differential regulation of CD36 transcription. This study indicates that CSCs may enjoy blood perfusion to maintain their stemness features. Targeting the LPA/PKD-1 -CD36 signaling pathway may have therapeutic potential to curb tumor progression by disrupting the arteriolar niche and effectively eliminating CSCs.
    Keyword
    arteriolar niche
    breast cancer stem cells
    Breast Neoplasms
    Cell Self Renewal
    Lysophospholipids
    Protein Kinase D
    Signal Transduction
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/16119
    ae974a485f413a2113503eed53cd6c53
    10.1038/s42003-021-02308-6
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