2026-04-22T20:10:44Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/97922024-12-18T01:05:24Zcom_10259_6168com_10259_5086com_10259_2604col_10259_6169

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. 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