De novo and cell line models of human mammary cell transformation reveal an essential role for Yb-1 in multiple stages of human breast cancer
In: Cell Death & Differentiation, Jg. 29 (2021-07-22), S. 54-64
Online
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Zugriff:
Breast cancer heterogeneity has made it challenging to identify mechanisms critical to the initial stages of their genesis in vivo. Here, we sought to interrogate the role of YB-1 in newly arising human breast cancers as well as in established cell lines. In a first series of experiments, we found that short-hairpin RNA-mediated knockdown of YB-1 in MDA-MB-231 cells blocked both their local tumour-forming and lung-colonising activity in immunodeficient mice. Conversely, upregulated expression of YB-1 enhanced the poor in vivo tumorigenicity of T47D cells. We then found that YB-1 knockdown also inhibits the initial generation in mice of invasive ductal carcinomas and ductal carcinomas in situ from freshly isolated human mammary cells transduced, respectively, with KRASG12D or myristoylated-AKT1. Interestingly, increased expression of HIF1α and G3BP1, two YB-1 translational targets and elements of a stress-adaptive programme, mirrored the levels of YB-1 in both transformed primary and established MDA-MB-231 breast cancer cells.
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De novo and cell line models of human mammary cell transformation reveal an essential role for Yb-1 in multiple stages of human breast cancer
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Autor/in / Beteiligte Person: | Hirst, Martin ; Colborne, Shane ; Eaves, Connie J. ; Pellacani, Davide ; Morin, Gregg B. ; El-Naggar, Amal ; Gian Luca Negri ; Lefort, Sylvain ; Tan, Susanna ; Gusterson, Barry A. ; Sorensen, Poul H. |
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Zeitschrift: | Cell Death & Differentiation, Jg. 29 (2021-07-22), S. 54-64 |
Veröffentlichung: | Springer Science and Business Media LLC, 2021 |
Medientyp: | unknown |
ISSN: | 1476-5403 (print) ; 1350-9047 (print) |
DOI: | 10.1038/s41418-021-00836-6 |
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