Title | Bone vascular niche E-selectin induces mesenchymal-epithelial transition and Wnt activation in cancer cells to promote bone metastasis. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Esposito, 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 |
Journal | Nat Cell Biol |
Volume | 21 |
Issue | 5 |
Pagination | 627-639 |
Date Published | 2019 May |
ISSN | 1476-4679 |
Keywords | Animals, 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> |
DOI | 10.1038/s41556-019-0309-2 |
Alternate Journal | Nat Cell Biol |
PubMed ID | 30988423 |
PubMed Central ID | PMC6556210 |
Grant List | P01 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 |