Bone vascular niche E-selectin induces mesenchymal–epithelial transition and Wnt activation in cancer cells to promote bone metastasis

Mark Esposito, Nandini Mondal, Todd M. Greco, Yong Wei, Chiara Spadazzi, Song Chang Lin, Hanqiu Zheng, Corey Cheung, John L. Magnani, Sue Hwa Lin, Ileana M. Cristea, Robert Sackstein, Yibin Kang

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26 Scopus citations

Abstract

How disseminated tumour cells engage specific stromal components in distant organs for survival and outgrowth is a critical but poorly understood step of the metastatic cascade. Previous studies have demonstrated the importance of the epithelial–mesenchymal transition in promoting the cancer stem cell properties needed for metastasis initiation, whereas the reverse process of mesenchymal–epithelial transition is required for metastatic outgrowth. Here we report that this paradoxical requirement for the simultaneous induction of both mesenchymal–epithelial transition and cancer stem cell traits in disseminated tumour cells is provided by bone vascular niche E-selectin, whose direct binding to cancer cells promotes bone metastasis by inducing mesenchymal–epithelial transition and activating Wnt signalling. E-selectin binding activity mediated by the α1-3 fucosyltransferases Fut3/Fut6 and Glg1 are instrumental to the formation of bone metastasis. These findings provide unique insights into the functional role of E-selectin as a component of the vascular niche critical for metastatic colonization in bone.

Original languageEnglish (US)
Pages (from-to)627-639
Number of pages13
JournalNature cell biology
Volume21
Issue number5
DOIs
StatePublished - May 1 2019

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Esposito, M., Mondal, N., Greco, T. M., Wei, Y., Spadazzi, C., Lin, S. C., Zheng, H., Cheung, C., Magnani, J. L., Lin, S. H., Cristea, I. M., Sackstein, R., & Kang, Y. (2019). Bone vascular niche E-selectin induces mesenchymal–epithelial transition and Wnt activation in cancer cells to promote bone metastasis. Nature cell biology, 21(5), 627-639. https://doi.org/10.1038/s41556-019-0309-2