Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis

Amal M. El-Naggar, Chansey J. Veinotte, Hongwei Cheng, Thomas G.P. Grunewald, Gian Luca Negri, Syam Prakash Somasekharan, Dale P. Corkery, Franck Tirode, Joan Mathers, Debjit Khan, Alastair H. Kyle, Jennifer H. Baker, Nancy E. LePard, Steven McKinney, Shamil Hajee, Momir Bosiljcic, Gabriel Leprivier, Cristina E. Tognon, Andrew I. Minchinton, Kevin L. BennewithOlivier Delattre, Yuzhuo Wang, Graham Dellaire, Jason N. Berman, Poul H. Sorensen

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)682-697
Number of pages16
JournalCancer Cell
Volume27
Issue number5
DOIs
StatePublished - May 11 2015
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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