|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|
|Date Published||2019 Apr 15|
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.
|Alternate Journal||Nat. Cell Biol.|