From Proteomic Analysis to Potential Therapeutic Targets: Functional Profile of Two Lung Cancer Cell Lines, A549 and SW900, Widely Studied in Pre-Clinical Research.
Lung cancer is a serious health problem and the leading cause of cancer death worldwide. The standard use of cell lines as in vitro pre-clinical 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 IIα 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.
Cancer Cell Biology Research Group, Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona, Campus Bellvitge, Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Spain.|Laboratory of Signal Transduction, Department of Medical Sciences, Institute for Research in Biomedicine-iBiMED, Health Sciences Program, University of Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.
Luís
http://orcid.org/0000-0002-2811-8081
L
Korrodi-Gregório
Cancer Cell Biology Research Group, Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona, Campus Bellvitge, Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Spain.
Vanessa
V
Soto-Cerrato
Department of Medical Sciences, Institute for Research in Biomedicine-iBiMED, Health Sciences Program, University of Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.|Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
Rui
R
Vitorino
Laboratory of Signal Transduction, Department of Medical Sciences, Institute for Research in Biomedicine-iBiMED, Health Sciences Program, University of Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.
Margarida
M
Fardilha
Cancer Cell Biology Research Group, Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona, Campus Bellvitge, Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Spain.
Ricardo
R
Pérez-Tomás
D000072283:A549 Cells / Q000187:drug effects* / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000075687:NEDD8 Protein; D050779:Nuclear Factor 90 Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology; D014452:Ubiquitins / Q000378:metabolism
D000075687:NEDD8 Protein; D050779:Nuclear Factor 90 Proteins; D019869:Phosphatidylinositol 3-Kinases; D018809:Proliferating Cell Nuclear Antigen; D020543:Proteome; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D059005:Topoisomerase II Inhibitors; D014452:Ubiquitins; C082860:NEDD8 protein, human; C546842:MTOR protein, human