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. Bennewith; Olivier Delattre; Yuzhuo Wang; Graham Dellaire; Jason N. Berman; Poul H. Sorensen

doi:10.1016/j.ccell.2015.04.003

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 journal › Article › peer-review

213 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 language	English (US)
Pages (from-to)	682-697
Number of pages	16
Journal	Cancer Cell
Volume	27
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2015.04.003
State	Published - May 11 2015
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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El-Naggar, A. M., Veinotte, C. J., Cheng, H., Grunewald, T. G. P., Negri, G. L., Somasekharan, S. P., Corkery, D. P., Tirode, F., Mathers, J., Khan, D., Kyle, A. H., Baker, J. H., LePard, N. E., McKinney, S., Hajee, S., Bosiljcic, M., Leprivier, G., Tognon, C. E., Minchinton, A. I., ... Sorensen, P. H. (2015). Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis. Cancer Cell, 27(5), 682-697. https://doi.org/10.1016/j.ccell.2015.04.003

El-Naggar, AM, Veinotte, CJ, Cheng, H, Grunewald, TGP, Negri, GL, Somasekharan, SP, Corkery, DP, Tirode, F, Mathers, J, Khan, D, Kyle, AH, Baker, JH, LePard, NE, McKinney, S, Hajee, S, Bosiljcic, M, Leprivier, G, Tognon, CE, Minchinton, AI, Bennewith, KL, Delattre, O, Wang, Y, Dellaire, G, Berman, JN & Sorensen, PH 2015, 'Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis', Cancer Cell, vol. 27, no. 5, pp. 682-697. https://doi.org/10.1016/j.ccell.2015.04.003

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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.}",

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doi = "10.1016/j.ccell.2015.04.003",

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AU - El-Naggar, Amal M.

AU - Veinotte, Chansey J.

AU - Cheng, Hongwei

AU - Grunewald, Thomas G.P.

AU - Negri, Gian Luca

AU - Somasekharan, Syam Prakash

AU - Corkery, Dale P.

AU - Tirode, Franck

AU - Mathers, Joan

AU - Khan, Debjit

AU - Kyle, Alastair H.

AU - Baker, Jennifer H.

AU - LePard, Nancy E.

AU - McKinney, Steven

AU - Hajee, Shamil

AU - Bosiljcic, Momir

AU - Leprivier, Gabriel

AU - Tognon, Cristina E.

AU - Minchinton, Andrew I.

AU - Bennewith, Kevin L.

AU - Delattre, Olivier

AU - Wang, Yuzhuo

AU - Dellaire, Graham

AU - Berman, Jason N.

AU - Sorensen, Poul H.

PY - 2015/5/11

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N2 - 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

Abstract

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