1. Bone vascular niche E-selectin induces mesenchymal–epithelial transition and Wnt activation in cancer cells to promote bone metastasis
- Author
-
John L. Magnani, Ileana M. Cristea, Nandini Mondal, Corey Cheung, Sue Hwa Lin, Todd M. Greco, Hanqiu Zheng, Yibin Kang, Song Chang Lin, Yong Wei, Chiara Spadazzi, Robert Sackstein, Mark Esposito, 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., and Kang Y.
- Subjects
Transcriptional Activation ,Epithelial-Mesenchymal Transition ,Stromal cell ,Bone Neoplasm ,Biology ,Metastasis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Fucosyltransferase ,Cancer stem cell ,Cell Line, Tumor ,medicine ,Mesenchymal–epithelial transition ,Epithelial–mesenchymal transition ,Stem Cell Niche ,Sialoglycoprotein ,Wnt Signaling Pathway ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,Animal ,Wnt signaling pathway ,Bone metastasis ,Cell Biology ,medicine.disease ,Receptors, Fibroblast Growth Factor ,Xenograft Model Antitumor Assays ,Cell biology ,Neoplasm Metastasi ,030220 oncology & carcinogenesis ,Cancer cell ,Neoplasm ,Neoplastic Stem Cell ,E-Selectin ,Human ,Signal Transduction - 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.
- Published
- 2019