2026-04-22T20:11:22Zhttps://riubu.ubu.es/oai/request

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

00925njm 22002777a 4500 dc Creedon, Helen author Gómez Cuadrado, Laura author Tarnauskaitė, Žygimantė author Balla, Jozef author Canel, Marta author MacLeod, Kenneth G. author Serrels, Bryan author Fraser, Craig author Unciti-Broceta, Asier author Tracey, Natasha author Le Bihan, Thierry author Kilnowska, Teresa author Sims, Andrew H. author Byron, Adam author Brunton, Valerie G. author 2016-02 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. http://hdl.handle.net/10259/9792 10.18632/oncotarget.7317 1949-2553 Resistance Breast cancer EMT HER2 Proteomics Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy