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Identification of a Key Co-Operative Role of YB-1 in the Genesis and Metastasis of Human Breast Cancer

By Sylvain Lefort, Amal El-Naggar, Susanna Tan, Shane Colborne, Gian Luca Negri, Davide Pellacani, Martin Hirst, Barry Gusterson, Gregg B Morin, Poul H Sorensen, Connie J Eaves

Posted 19 Jul 2018
bioRxiv DOI: 10.1101/372524

Shared mechanisms driving the malignant properties of human breast cancers have been difficult to identify because of their extensive biological and molecular heterogeneity. Here we sought to examine the possibility that mammalian Y-box binding protein-1 (YB-1) might have such a role given its association with poor survival in patients with other types of metastatic tumours[1][1],[2][2] and recently reported ability in high-risk sarcomas to induce a hypoxia-inducible factor 1α (HIF1α) response[3][3] and stress granule formation through translational activation of G3BP1 mRNAs[4][4]. However, the role of YB-1 in contributing to the malignant properties of human breast cancer cells in vivo has not been experimentally investigated. Here we demonstrate a critical co-operative role of YB-1 in mediating the initial as well as later malignant properties and downstream activities displayed by de novo transformed normal human mammary cells as well as by an established aggressive breast cancer cell line in transplanted immunodeficient mice. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4

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