Abstract
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.
Highlights
Cancer is a heterogeneous group of diseases that results from abnormal, autonomous and uncontrolled cell growth and differentiation, promoting tumor formation and metastasis
Restauration of transcripts, p16INK4α in the A549 cell line, leads to suppression of cell growth and enhanced sensitivity to cisplatinum, the first-line treatment for many lung cancers [12]. Both cell lines harbor an activating mutation in Rat Sarcoma (RAS) pro-oncogene K-Ras protein (SW900 is heterozygous for c.35G>T/p.G12V and A549 is homozygous for c.34G>A/p.G12S) that belongs to the small GTPase superfamily[14]
This keratin is an intermediate filament cytokeratin that is commonly associated with simple epithelium and is highly abundant in lung adenocarcinoma when comparing with squamous carcinoma[39, 40]
Summary
Cancer is a heterogeneous group of diseases that results from abnormal, autonomous and uncontrolled cell growth and differentiation, promoting tumor formation and metastasis. By using label-free MS, the protein expression of these two lung cancer cell lines, adenocarcinoma (A549) and squamous carcinoma (SW900), was studied and the differences from the two major subtypes of lung cancer are presented. To our knowledge, this is the first time that a proteomic comparison between the two most frequent lung cancer subtypes has been performed. These results will be useful for a better understanding of the cell biology of the main subtypes of lung cancer and can be used in future studies to develop targeted antitumoral therapies
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