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El-Naggar, Amal M.; Veinotte, Chansey J.; Cheng, Hongwei; Grunewald, Thomas G.P.; Negri, Gian Luca; Somasekharan, Syam Prakash; Corkery, Dale P.; Tirode, Franck; Mathers, Joan; Khan, Debjit; Kyle, Alastair H.; Baker, Jennifer H.; LePard, Nancy E.; McKinney, Steven; Hajee, Shamil; Bosiljcic, Momir; Leprivier, Gabriel; Tognon, Cristina E.; Minchinton, Andrew I.; Bennewith, Kevin L.; Delattre, Olivier; Wang, Yuzhuo; Dellaire, Graham; Berman, Jason N.; Sorensen, Poul H.
Cancer cell, 05/2015, Letnik: 27, Številka: 5Journal Article
Metastatic dissemination is the leading cause of death in cancer patients, which is particularly evident for high-risk sarcomas such as Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma. Previous research identified a crucial role for YB-1 in the epithelial-to-mesenchymal transition (EMT) and metastasis of epithelial malignancies. Based on clinical data and two distinct animal models, we now report that YB-1 is also a major metastatic driver in high-risk sarcomas. Our data establish YB-1 as a critical regulator of hypoxia-inducible factor 1α (HIF1α) expression in sarcoma cells. YB-1 enhances HIF1α protein expression by directly binding to and activating translation of HIF1A messages. This leads to HIF1α-mediated sarcoma cell invasion and enhanced metastatic capacity in vivo, highlighting a translationally regulated YB-1-HIF1α axis in sarcoma metastasis. Display omitted •YB-1 expression is elevated in high-risk human sarcomas•YB-1 promotes sarcoma invasion and metastasis•YB-1 regulates HIF1α expression by directly promoting its mRNA translation•YB-1 effects on sarcoma invasion and metastasis are mediated by HIF1α YB-1 binds DNA and RNA and has been shown to promote epithelial-to-mesenchymal transition and metastasis of carcinomas. El-Naggar et al. show that YB-1 also contributes to metastasis of high-risk sarcomas by binding to HIF1A mRNA and enhancing its translation.
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in: SICRIS
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