2026-04-22T20:10:54Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/97922024-12-18T01:05:24Zcom_10259_6168com_10259_5086com_10259_2604col_10259_6169
Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy
Creedon, Helen
Gómez Cuadrado, Laura
Tarnauskaitė, Žygimantė
Balla, Jozef
Canel, Marta
MacLeod, Kenneth G.
Serrels, Bryan
Fraser, Craig
Unciti-Broceta, Asier
Tracey, Natasha
Le Bihan, Thierry
Kilnowska, Teresa
Sims, Andrew H.
Byron, Adam
Brunton, Valerie G.
Resistance
Breast cancer
EMT
HER2
Proteomics
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.
2024-12-17
2024-12-17
2016-02
info:eu-repo/semantics/article
http://hdl.handle.net/10259/9792
10.18632/oncotarget.7317
1949-2553
eng
Oncotarget. 2016, V. 7, n. 10, p. 11539-11552
https://doi.org/10.18632/oncotarget.7317
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Atribución 4.0 Internacional
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