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

Mark Esposito, Nandini Mondal, Todd M Greco, Yong Wei, Chiara Spadazzi, Song-Chang Lin, Hanqiu Zheng, Corey Cheung, John L Magnani, Sue-Hwa Lin, Ileana M Cristea, Robert Sackstein, Yibin Kang

Nature cell biology 2019 May

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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.

Citation

Mark Esposito, Nandini Mondal, Todd M Greco, Yong Wei, Chiara Spadazzi, Song-Chang Lin, Hanqiu Zheng, Corey Cheung, John L Magnani, Sue-Hwa Lin, Ileana M Cristea, Robert Sackstein, Yibin Kang. Bone vascular niche E-selectin induces mesenchymal-epithelial transition and Wnt activation in cancer cells to promote bone metastasis. Nature cell biology. 2019 May;21(5):627-639