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

TitleBone vascular niche E-selectin induces mesenchymal-epithelial transition and Wnt activation in cancer cells to promote bone metastasis.
Publication TypeJournal Article
Year of Publication2019
AuthorsEsposito, M, Mondal, N, Greco, TM, Wei, Y, Spadazzi, C, Lin, S-C, Zheng, H, Cheung, C, Magnani, JL, Lin, S-H, Cristea, IM, Sackstein, R, Kang, Y
JournalNat Cell Biol
Volume21
Issue5
Pagination627-639
Date Published2019 05
ISSN1476-4679
KeywordsAnimals, Bone Neoplasms, Cell Line, Tumor, Cell Movement, Cell Proliferation, E-Selectin, Epithelial-Mesenchymal Transition, Fucosyltransferases, Humans, Mice, Neoplasm Metastasis, Neoplasms, Neoplastic Stem Cells, Receptors, Fibroblast Growth Factor, Sialoglycoproteins, Signal Transduction, Stem Cell Niche, Transcriptional Activation, Wnt Signaling Pathway, Xenograft Model Antitumor Assays
Abstract

<p>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.</p>

DOI10.1038/s41556-019-0309-2
Alternate JournalNat. Cell Biol.
PubMed ID30988423
PubMed Central IDPMC6556210
Grant ListP01 HL107146 / HL / NHLBI NIH HHS / United States
P30 CA072720 / CA / NCI NIH HHS / United States
R01 CA212410 / CA / NCI NIH HHS / United States
R01 CA141062 / CA / NCI NIH HHS / United States
F31 CA192461 / CA / NCI NIH HHS / United States