Quantitative Phosphoproteomic Analysis Reveals Key Mechanisms of Cellular Proliferation in Liver Cancer Cells

Understanding the mechanisms of uncontrolled proliferation in cancer cells provides valuable insights into tumor development and is benefit for discovering efficient methods in cancer treatment. In this study, we identified and quantified 2,057 phosphoproteins and 9,824 unique phosphosites in three liver cell lines with high (QGY, Hep3B) and low (L02) proliferative potentials and disclosed the wide variations in phosphorylation sites and levels among them. We found that the number of identified phosphoproteins and phosphosites in these cells were negatively correlated with their proliferative abilities. The function analysis suggested that the aberrant phosphorylation of SR proteins and activation of MAPK pathway might be two critical factors to promote cancer cell proliferation. Meanwhile, the phosphorylation status of mini-chromosome maintenance (MCM) and nuclear pore (NPC) complexes are significantly different between cell lines with high and low proliferative potentials. Furthermore, the phosphosites targeted by kinase families of CDK, STE and HIPK in the proteins coded by cancer driver genes showed distinct profiles between caner and normal cell lines. These results present key phosphorylation networks involving in abnormal proliferation of cancer cells and uncovered potential molecular markers for estimating the proliferation ability of liver cancer cells.