Quantitative Proteomic Approach to Understand Metabolic Adaptation in Non-Small Cell Lung Cancer
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- 作者：Alfonso Mart铆n-Bernab茅 ; Rold谩n Cort茅s ; Sylvia G. Lehmann ; Michel Seve ; Marta Cascante ; Sandrine Bourgoin-Voillard
- 刊名：Journal of Proteome Research
- 出版年：2014
- 出版时间：November 7, 2014
- 年：2014
- 卷：13
- 期：11
- 页码：4695-4704
- 全文大小：338K
- ISSN：1535-3907
文摘
KRAS mutations in non-small cell lung cancer (NSCLC) are a predictor of resistance to EGFR-targeted therapies. Because approaches to target RAS signaling have been unsuccessful, targeting lung cancer metabolism might help to develop a new strategy that could overcome drug resistance in such cancer. In this study, we applied a large screening quantitative proteomic analysis to evidence key enzymes involved in metabolic adaptations in lung cancer. We carried out the proteomic analysis of two KRAS-mutated NSCLC cell lines (A549 and NCI-H460) and a non tumoral bronchial cell line (BEAS-2B) using an iTRAQ (isobaric tags for relative and absolute quantitation) approach combined with two-dimensional fractionation (OFFGEL/RP nanoLC) and MALDI鈥揟OF/TOF mass spectrometry analysis. Protein targets identified by our iTRAQ approach were validated by Western blotting analysis. Among 1038 proteins identified and 834 proteins quantified, 49 and 82 proteins were respectively found differently expressed in A549 and NCI-H460 cells compared to the BEAS-2B non tumoral cell line. Regarding the metabolic pathways, enzymes involved in glycolysis (GAPDH/PKM2/LDH-A/LDH-B) and pentose phosphate pathway (PPP) (G6PD/TKT/6PGD) were up-regulated. The up-regulation of enzyme expression in PPP is correlated to their enzyme activity and will be further investigated to confirm those enzymes as promising metabolic targets for the development of new therapeutic treatments or biomarker assay for NSCLC.