In turn, the current presence of EGFR in the squamous carcinoma cell line may not confer any therapeutic advantage since this cell line comes with an activating mutation in K-RAS as well as the PI3K/Akt/mTOR route appears to be less energetic within this cell line. squamous carcinoma cell range. The protein-protein relationship network was extracted from HIPPIE and visualized in the Cytoscape software program. Edges stand for high confidence connections. Round nodes denotes protein extracted from MS, whereas gemstone nodes are protein extracted from HIPPIE data source. Node size SR9011 relates to the betweeness centrality (high betweeness centrality represent SR9011 essential nodes in the network, also called bottlenecks) from the proteins and was computed using the NetworkAnalyzer device. Node color is certainly depicted as pursuing (SW900 vs A549): green, protein upregulated (fold-regulation 2); reddish colored, proteins downregulated (fold-regulation -2); yellowish, unaltered protein; violet, SW900-particular protein.(TIF) pone.0165973.s003.tif (5.0M) GUID:?E53763D2-B9BF-4BDC-B7A6-33FD7649264F S1 Desk: A549 and SW900 protein obtained by MALDI-TOF/TOF. (XLSX) pone.0165973.s004.xlsx (96K) GUID:?6CBEA7E7-D72F-42A1-ABD1-8B4974D0963A S2 Desk: A549-particular genes mapped by DAVID and matching GOs conditions (mobile component, biological procedure and molecular function) linked considering a p-value of 0.05. (XLSX) pone.0165973.s005.xlsx (24K) GUID:?A6126032-4853-423A-9E88-742D02994AStomach S3 Desk: SW900-particular genes mapped by DAVID and corresponding GOs conditions (cellular element, biological procedure and molecular function) associated considering a p-value of 0.05. (XLSX) pone.0165973.s006.xlsx (27K) GUID:?5A733140-2F70-4D29-9867-2A3DE2EE0A45 S4 Desk: A549 context relevant protein-protein interactions (PPIs) with medium-high confidence (score 0.63) retrieved from Cd300lg HIPPIE data source. (XLSX) pone.0165973.s007.xlsx (1.5M) GUID:?2FD77A21-5989-4F6B-9054-7146D85C4576 S5 Desk: SW900 framework relevant protein-protein interactions (PPIs) with medium-high self-confidence (score 0.63) retrieved from HIPPIE database. (XLSX) pone.0165973.s008.xlsx (1.8M) GUID:?4F9CF6CF-0D89-4B4B-8CFC-4D95A85D024F Data Availability StatementAll relevant data are within the paper and its Supporting Information files. Abstract Lung cancer is a serious health problem and the leading cause of cancer death worldwide. The standard use of cell lines as pre-clinical SR9011 models to study the molecular mechanisms that drive tumorigenesis and access drug sensitivity/effectiveness is of undisputable importance. Label-free mass spectrometry and bioinformatics were employed to study the proteomic profiles of two representative lung cancer cell lines and to unravel the specific biological processes. Adenocarcinoma A549 cells were enriched in proteins related to cellular respiration, ubiquitination, apoptosis and response to drug/hypoxia/oxidative stress. In turn, squamous carcinoma SW900 cells were enriched in proteins related to translation, apoptosis, response to inorganic/organic substances and cytoskeleton organization. Several proteins with differential expression were related to cancer transformation, tumor resistance, proliferation, migration, invasion and metastasis. Combined analysis of proteome and interactome data highlighted key proteins and suggested that adenocarcinoma might be more prone to PI3K/Akt/mTOR and topoisomerase II inhibitors, and squamous carcinoma to Ck2 inhibitors. Moreover, ILF3 overexpression in adenocarcinoma, and PCNA and NEDD8 in squamous carcinoma shows them as promising candidates for therapeutic purposes. This study highlights the functional proteomic differences of two main subtypes of lung cancer models and hints several targeted therapies that might assist in this type of cancer. Introduction Cancer is a heterogeneous group of diseases that results from abnormal, autonomous and uncontrolled cell growth and differentiation, promoting tumor formation and metastasis. Tumors are commonly characterized by six hallmarks: insensitivity to anti-growth signals, evasion of apoptosis, self-sufficiency in growth signals, sustained angiogenesis, limitless replicative potential and tissue invasion and metastasis[1]. Moreover, there are two novel emerging hallmarks: deregulation of the cellular energetics and avoidance of immune destruction[2]. Signaling cascades, which usually control cellular homeostasis, are deregulated in tumorigenesis through genetic, epigenetic and somatic alterations[3]. Hence, the acquisition of these hallmarks is facilitated by an enabling characteristic of cancer cells: genomic instability[2]. Lung cancer is the world leading cause of cancer-related mortality in both genders. The 2012 estimated rates of the European Cancer Observatory (ECO), states that lung cancer contributed with one fifth of the total cancer-related deaths[4]. The main causes of lung cancer include tobacco smoke (direct or indirectly, account for more than 85%), asbestos, ionizing radiation (e.g. radon) and other air pollutants. Conversely, only 10% of smokers will develop lung cancer and not all exposed to the other environmental factors will develop it[5], highlighting the importance of intrinsic factors. At the histological level, lung cancer is divided into two major types: small-cell (SCLC) and non-small-cell lung carcinoma (NSCLC). SCLC accounts for around 12C15% of all cases, being however more aggressive and metastatic than NSCLC[6]. NSCLC is less aggressive and spreads more slowly but is more common, accounting for at least 85C88% of.