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Nat Cell Biol. 2019 May;21(5):627-639. doi: 10.1038/s41556-019-0309-2. Epub 2019 Apr 15.

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

Author information

1
Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
2
Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
3
Program of Excellence in Glycosciences, Harvard Medical School, Boston, MA, USA.
4
Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy.
5
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
6
Glycomimetics Inc., Gaithersburg, MD, USA.
7
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
8
Department of Molecular Biology, Princeton University, Princeton, NJ, USA. ykang@princeton.edu.

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.

Comment in

PMID:
30988423
PMCID:
PMC6556210
[Available on 2019-10-15]
DOI:
10.1038/s41556-019-0309-2
[Indexed for MEDLINE]

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