Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature cell biology, 2019-05, Vol.21 (5), p.627-639

Ort / Verlag

England

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.