| Literature DB >> 25965573 |
Amal M El-Naggar1, Chansey J Veinotte2, Hongwei Cheng3, Thomas G P Grunewald4, Gian Luca Negri1, Syam Prakash Somasekharan5, Dale P Corkery2, Franck Tirode6, Joan Mathers5, Debjit Khan5, Alastair H Kyle7, Jennifer H Baker7, Nancy E LePard7, Steven McKinney5, Shamil Hajee5, Momir Bosiljcic8, Gabriel Leprivier5, Cristina E Tognon5, Andrew I Minchinton7, Kevin L Bennewith8, Olivier Delattre6, Yuzhuo Wang3, Graham Dellaire9, Jason N Berman10, Poul H Sorensen11.
Abstract
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.Entities:
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Year: 2015 PMID： 25965573 DOI： 10.1016/j.ccell.2015.04.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743