Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis

doi:10.1016/j.ccell.2015.04.003

. 2015 May 11;27(5):682-97.

doi: 10.1016/j.ccell.2015.04.003.

Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis

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

Affiliations

¹ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Department of Molecular Oncology, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada.
² Department of Pediatrics, IWK Health Centre, Halifax, NS B3K 6R8, Canada.
³ Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
⁴ Laboratory for Pediatric Sarcoma Biology, Institute of Pathology, LMU Munich, Thalkirchner Strasse 36, 80337 Munich, Germany.
⁵ Department of Molecular Oncology, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada.
⁶ INSERM U830, Laboratoire de génétique et biologie des cancers, Institut Curie, 75248 Paris, France.
⁷ Department of Integrative Oncology, Radiation Biology Unit, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada.
⁸ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Department of Integrative Oncology, Radiation Biology Unit, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada.
⁹ Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
¹⁰ Department of Pediatrics, IWK Health Centre, Halifax, NS B3K 6R8, Canada; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada; Department of Pediatrics, Dalhousie University, Halifax, NS B3H 4R2, Canada.
¹¹ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Department of Molecular Oncology, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada. Electronic address: psor@mail.ubc.ca.

PMID: 25965573
DOI: 10.1016/j.ccell.2015.04.003

Free article

Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis

Amal M El-Naggar et al. Cancer Cell. 2015.

Free article

. 2015 May 11;27(5):682-97.

doi: 10.1016/j.ccell.2015.04.003.

Authors

Affiliations

¹ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Department of Molecular Oncology, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada.
² Department of Pediatrics, IWK Health Centre, Halifax, NS B3K 6R8, Canada.
³ Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
⁴ Laboratory for Pediatric Sarcoma Biology, Institute of Pathology, LMU Munich, Thalkirchner Strasse 36, 80337 Munich, Germany.
⁵ Department of Molecular Oncology, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada.
⁶ INSERM U830, Laboratoire de génétique et biologie des cancers, Institut Curie, 75248 Paris, France.
⁷ Department of Integrative Oncology, Radiation Biology Unit, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada.
⁸ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Department of Integrative Oncology, Radiation Biology Unit, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada.
⁹ Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
¹⁰ Department of Pediatrics, IWK Health Centre, Halifax, NS B3K 6R8, Canada; Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada; Department of Pediatrics, Dalhousie University, Halifax, NS B3H 4R2, Canada.
¹¹ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Department of Molecular Oncology, British Columbia Cancer Research Center, Vancouver, BC V5Z 1L3, Canada. Electronic address: psor@mail.ubc.ca.

PMID: 25965573
DOI: 10.1016/j.ccell.2015.04.003

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.

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Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis

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Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis

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