Development of an arteriolar niche and self-renewal of breast cancer stem cells by lysophosphatidic acid/protein kinase D signaling
Author
Jiang, YinanGuo, 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
Date
2021-06-24Journal
Communications BiologyPublisher
Springer NatureType
Article
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Show full item recordAbstract
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 nichebreast 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/10713/16119ae974a485f413a2113503eed53cd6c53
10.1038/s42003-021-02308-6
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