2026-04-23T00:07:25Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/97922024-12-18T01:05:24Zcom_10259_6168com_10259_5086com_10259_2604col_10259_6169
Creedon, Helen
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Gómez Cuadrado, Laura
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Tarnauskaitė, Žygimantė
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Balla, Jozef
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Canel, Marta
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MacLeod, Kenneth G.
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Serrels, Bryan
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Fraser, Craig
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Unciti-Broceta, Asier
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Tracey, Natasha
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Le Bihan, Thierry
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Kilnowska, Teresa
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Sims, Andrew H.
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Byron, Adam
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Brunton, Valerie G.
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2024-12-17T09:28:07Z
2024-12-17T09:28:07Z
2016-02
http://hdl.handle.net/10259/9792
10.18632/oncotarget.7317
1949-2553
Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies in the treatment of HER2-positive breast cancer is a major clinical problem. To identify pathways linked to resistance, we generated HER2-positive breast cancer cell lines which are resistant to either lapatinib or AZD8931, two pan-HER family kinase inhibitors. Resistance was HER2 independent and was associated with epithelial-to-mesenchymal transition (EMT), resulting in increased proliferation and migration of the resistant cells. Using a global proteomics approach, we identified a novel set of EMT-associated proteins linked to HER2-independent resistance. We demonstrate that a subset of these EMT-associated genes is predictive of prognosis within the ERBB2 subtype of human breast cancers. Furthermore, targeting the EMT-associated kinases Src and Axl potently inhibited proliferation of the resistant cells, and inhibitors to these kinases may provide additional options for the treatment of HER2-independent resistance in tumors.
This work was supported by Cancer Research UK grants (C157/A15703 and C6088/A12063). The mass spectrometer was funded by a Wellcome Trust Institutional Strategic Support Fund award and a Wellcome Trust Strategic Award to the University of Edinburgh Centre for Immunity, Infection and Evolution. SynthSys is a Centre for Integrative Systems Biology funded by the Biotechnology and Biological Sciences Research Council and Engineering and Physical Sciences Research Council (reference BB/D019621/1).
application/pdf
eng
Impact Journals
Oncotarget. 2016, V. 7, n. 10, p. 11539-11552
https://doi.org/10.18632/oncotarget.7317
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Resistance
Breast cancer
EMT
HER2
Proteomics
Salud
Medicina
Oncología
Health
Medicine
Oncology
Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Oncotarget
7
10
11539
11552
THUMBNAIL
Creedon-oncotarget_2016.pdf.jpg
Creedon-oncotarget_2016.pdf.jpg
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LICENSE
license.txt
license.txt
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https://riubu.ubu.es/bitstream/10259/9792/3/license.txt
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ORIGINAL
Creedon-oncotarget_2016.pdf
Creedon-oncotarget_2016.pdf
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10259/9792
oai:riubu.ubu.es:10259/9792
2024-12-18 02:05:24.993
Repositorio Institucional de la Universidad de Burgos
bubrep@ubu.es
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