Title: Phosphoproteomic and proteomic identification of oncogenic pathways in LKB1 dependent non-small cell lung cancer by two-dimensional LC-MS/MS

摘要

Lung cancer is one of the main causes of cancer related deaths worldwide. This is a field of study that remains open for discovery based scientific research due to the complexity of the condition and the low five-year survival rate. Proteomic profiling of cancer cell lines can be used to identify potentially useful protein biomarkers and to reveal the connectivity between oncogenic pathways that may facilitate the drug discovery process. Liver kinase B1 (LKB1) is a tumor suppressor gene and a key metabolic regulator found in cells.1 However, somatic mutations of LKB1 lead to loss of its expression in lung tissues as found in about 30-40% of non-small cell lung tumors (NSCLC). The LKB1-dependent signaling events are mediated mainly by AMP-activated protein kinase (AMPK) pathway.1 However, the transcription level changes of multi-pathway proteins indicates the influence of LKB1 mutations at a much deeper level in the tissue proteome,2 leaving the comprehensive mechanism and relationship of LKB1 to NSCLC unclear. Here, we present our study on identifying these pathways based on differential regulation of phosphoproteins, proteins, and localization of phosphorylation events by label-free proteomics. We used two-dimensional liquid chromatography coupled to tandem mass spectrometry (2D LC-MS/MS) to discover these changes during tumorigenesis in cell lines.