Novel pathways involved in cisplatin resistance identified by a proteomics approach in non-small-cell lung cancer cells

Research output: Contribution to journalArticle

Abstract

Although platinum-based chemotherapy remains the standard-of-care for most patients with advanced non-small-cell lung cancer (NSCLC), acquired resistance occurs frequently predicting poor prognosis. To examine the mechanisms underlying platinum resistance, we have generated and characterized by proteomic approach the resistant A549 CDDP-resistant (CPr-A549) and their parental A549 cells, identifying 15 proteins differentially expressed (13 upregulated and 2 downregulated in CPr-A549). In details, we highlighted a coherent network of proteins clustering together and involved in altered protein folding and endoplasmic reticulum stress, correlated with epithelial to mesenchymal transition process and cancer stem cell markers, where vimentin played a hierarchical role, ultimately resulting in increased aggressive features. By using publicly available databases we showed that the modulated proteins could contribute to NSCLC carcinogenesis and correlate with NSCLC patients prognosis and survival probability, suggesting that they can be used as novel potential prognostic/predictive biomarkers or therapeutic targets to overcome platinum-resistance.

Original languageEnglish
Pages (from-to)9077-9092
Number of pages16
JournalJournal of Cellular Physiology
Volume234
Issue number6
DOIs
Publication statusPublished - Jun 2019

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Platinum
Non-Small Cell Lung Carcinoma
Proteomics
Cisplatin
Proteins
Endoplasmic Reticulum Stress
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
Protein Folding
Vimentin
Standard of Care
Cluster Analysis
Carcinogenesis
Down-Regulation
Biomarkers
Databases
Drug Therapy
Survival
Therapeutics

Cite this

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title = "Novel pathways involved in cisplatin resistance identified by a proteomics approach in non-small-cell lung cancer cells",
abstract = "Although platinum-based chemotherapy remains the standard-of-care for most patients with advanced non-small-cell lung cancer (NSCLC), acquired resistance occurs frequently predicting poor prognosis. To examine the mechanisms underlying platinum resistance, we have generated and characterized by proteomic approach the resistant A549 CDDP-resistant (CPr-A549) and their parental A549 cells, identifying 15 proteins differentially expressed (13 upregulated and 2 downregulated in CPr-A549). In details, we highlighted a coherent network of proteins clustering together and involved in altered protein folding and endoplasmic reticulum stress, correlated with epithelial to mesenchymal transition process and cancer stem cell markers, where vimentin played a hierarchical role, ultimately resulting in increased aggressive features. By using publicly available databases we showed that the modulated proteins could contribute to NSCLC carcinogenesis and correlate with NSCLC patients prognosis and survival probability, suggesting that they can be used as novel potential prognostic/predictive biomarkers or therapeutic targets to overcome platinum-resistance.",
author = "Milone, {Maria Rita} and Rita Lombardi and Roca, {Maria Serena} and Francesca Bruzzese and Laura Addi and Biagio Pucci and Alfredo Budillon",
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T1 - Novel pathways involved in cisplatin resistance identified by a proteomics approach in non-small-cell lung cancer cells

AU - Milone, Maria Rita

AU - Lombardi, Rita

AU - Roca, Maria Serena

AU - Bruzzese, Francesca

AU - Addi, Laura

AU - Pucci, Biagio

AU - Budillon, Alfredo

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AB - Although platinum-based chemotherapy remains the standard-of-care for most patients with advanced non-small-cell lung cancer (NSCLC), acquired resistance occurs frequently predicting poor prognosis. To examine the mechanisms underlying platinum resistance, we have generated and characterized by proteomic approach the resistant A549 CDDP-resistant (CPr-A549) and their parental A549 cells, identifying 15 proteins differentially expressed (13 upregulated and 2 downregulated in CPr-A549). In details, we highlighted a coherent network of proteins clustering together and involved in altered protein folding and endoplasmic reticulum stress, correlated with epithelial to mesenchymal transition process and cancer stem cell markers, where vimentin played a hierarchical role, ultimately resulting in increased aggressive features. By using publicly available databases we showed that the modulated proteins could contribute to NSCLC carcinogenesis and correlate with NSCLC patients prognosis and survival probability, suggesting that they can be used as novel potential prognostic/predictive biomarkers or therapeutic targets to overcome platinum-resistance.

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