Journal
CANCER CELL
Volume 27, Issue 5, Pages 682-697Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2015.04.003
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Funding
- British Columbia Cancer Foundation
- Terry Fox Research Institute [1021]
- Collaborative Health Research Project grant from the Canadian Institutes of Health Research and Natural Science and Engineering Research Council
- Ewings Cancer Foundation of Canada [C17]
- Childhood Cancer Canada Foundation
- Coast to Coast Against Cancer Foundation
- Egyptian government
- Beatrice Hunter Cancer Research Institute
- Canadian Institutes of Health Research
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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 1 alpha (HIF1 alpha) expression in sarcoma cells. YB-1 enhances HIF1 alpha protein expression by directly binding to and activating translation of HIF1A messages. This leads to HIF1 alpha-mediated sarcoma cell invasion and enhanced metastatic capacity in vivo, highlighting a translationally regulated YB-1-HIF1 alpha axis in sarcoma metastasis.
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