@article{127b8d2b4aae4fdebb956ba000781924,
title = "Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis",
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.",
author = "El-Naggar, {Amal M.} and Veinotte, {Chansey J.} and Hongwei Cheng and Grunewald, {Thomas G.P.} and Negri, {Gian Luca} and Somasekharan, {Syam Prakash} and Corkery, {Dale P.} and Franck Tirode and Joan Mathers and Debjit Khan and Kyle, {Alastair H.} and Baker, {Jennifer H.} and LePard, {Nancy E.} and Steven McKinney and Shamil Hajee and Momir Bosiljcic and Gabriel Leprivier and Tognon, {Cristina E.} and Minchinton, {Andrew I.} and Bennewith, {Kevin L.} and Olivier Delattre and Yuzhuo Wang and Graham Dellaire and Berman, {Jason N.} and Sorensen, {Poul H.}",
note = "Funding Information: We thank Drs. Valentina Evdokimova, Greg Goodall, Thilo Hagen, Peggy Olive, Catherine Pallen, Torsten Nielsen, Corinna Warburton, Yuanmei Lou, Steven Poon, Amy Li, and Brian Kwok for reagents, technical assistance, and helpful discussions. This work was supported by funds from the British Columbia Cancer Foundation through Team Finn and other generous riders in the Ride to Conquer Cancer (to P.H.S.), from Terry Fox Research Institute Team Grant 1021 (to P.H.S.), a Collaborative Health Research Project grant from the Canadian Institutes of Health Research and Natural Science and Engineering Research Council (to G.D. and J.N.B.), and support from C 17 funding by the Ewings Cancer Foundation of Canada, Childhood Cancer Canada Foundation, and the Coast to Coast Against Cancer Foundation. A.M.E. was funded through a graduate scholarship from the Egyptian government, and D.P.C. was funded by the Beatrice Hunter Cancer Research Institute. K.L.B., a Michael Smith Foundation for Health Research Biomedical Research Scholar, was funded from the Canadian Institutes of Health Research. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = may,
day = "11",
doi = "10.1016/j.ccell.2015.04.003",
language = "English (US)",
volume = "27",
pages = "682--697",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}