Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry

Autor: Álvaro Quintanal-Villalonga, Maria Dolores Pastor, Ángela Marrugal, Laura Ojeda, Irene Ferrer, Amancio Carnero, Sonia Molina-Pinelo, Luis Paz-Ares
Přispěvatelé: Comunidad de Madrid, European Regional Development Fund, Fundación Mutua Madrileña, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Commission, Junta de Andalucía, Asociación Española Contra el Cáncer, Ministerio de Economía y Competitividad (España), Fundación Científica Asociación Española Contra el Cáncer, Ministerio de Educación, Cultura y Deporte (España)
Rok vydání: 2019
Předmět:
Zdroj: Repisalud
Instituto de Salud Carlos III (ISCIII)
Cells
Cells, Vol 8, Iss 8, p 806 (2019)
Digital.CSIC. Repositorio Institucional del CSIC
instname
Volume 8
Issue 8
ISSN: 0046-2012
Popis: Heat shock protein 90 (HSP90) is an important chaperone in lung adenocarcinoma, with relevant protein drivers such as EGFR (epidermal growth factor receptor) and EML4-ALK (echinoderm microtubule-associated protein-like protein4 fused to anaplastic lymphoma kinase) depending on it for their correct function, therefore HSP90 inhibitors show promise as potential treatments for lung adenocarcinoma. To study responses to its inhibition, HSP90 was pharmacologically interrupted by geldanamycin and resorcinol derivatives or with combined inhibition of HSP90 plus HSP70 in lung adenocarcinoma cell lines. Two-dimensional electrophoresis was performed to identify proteomic profiles associated with inhibition which will help to understand the biological basis for the responses. HSP90 inhibition resulted in altered protein profiles that differed according the treatment condition studied. Results revealed 254 differentially expressed proteins after treatments, among which, eukaryotic translation initiation factor3 subunit I (eIF3i) and citrate synthase demonstrated their potential role as response biomarkers. The differentially expressed proteins also enabled signalling pathways involved in responses to be identified; these included apoptosis, serine-glycine biosynthesis and tricarboxylic acid cycle. The proteomic profiles identified here contribute to an improved understanding of HSP90 inhibition and open possibilities for the detection of potential response biomarkers which will be essential to maximize treatment efficacy in lung adenocarcinoma.
L.P.A. was funded by the Comunidad de Madrid, CAM, (B2017/BMD3884), ISCIII (PIE15/00076, PI17/00778 and DTS17/00089) and CIBERONC (CB16/12/00442), and co-funded by FEDER from Regional Development European Funds (European Union). S.M.P. is funded by the Fundación Mutua Madrileña (2014) Ministry of Health and Social Welfare of Junta de Andalucía (PI-0046-2012, Nicolas Monardes Program C-0040-2016), ISCIII (PI17/00033), and co-funded by FEDER from Regional Development European Funds (European Union). I.F. is funded by the AECC (AIO2015) and ISCIII (PI16/01311), and co-funded by FEDER from Regional Development European Funds (European Union). AC was funded by grants from the Spanish Ministry of Economy and Competitiveness Plan Estatal de I+D+I 2018 co-funded by FEDER: RTI2018-097455-B-I00; CIBER de Cáncer (CB16/12/00275), co-funded by FEDER from Regional Development European Funds. Especial thanks to the Fundación AECC. L.O. is funded by the Ministerio de Educación, Cultura y Deporte (FPU13/02595).
Databáze: OpenAIRE
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