RT info:eu-repo/semantics/article
T1 Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy
A1 Creedon, Helen
A1 Gómez Cuadrado, Laura
A1 Tarnauskaitė, Žygimantė
A1 Balla, Jozef
A1 Canel, Marta
A1 MacLeod, Kenneth G.
A1 Serrels, Bryan
A1 Fraser, Craig
A1 Unciti-Broceta, Asier
A1 Tracey, Natasha
A1 Le Bihan, Thierry
A1 Kilnowska, Teresa
A1 Sims, Andrew H.
A1 Byron, Adam
A1 Brunton, Valerie G.
K1 Resistance
K1 Breast cancer
K1 EMT
K1 HER2
K1 Proteomics
K1 Salud
K1 Health
K1 Medicina
K1 Medicine
K1 Oncología
K1 Oncology
AB 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.
PB Impact Journals
YR 2016
FD 2016-02
LK http://hdl.handle.net/10259/9792
UL http://hdl.handle.net/10259/9792
LA eng
NO 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).
DS Repositorio Institucional de la Universidad de Burgos
RD 22-dic-2024