Differently expressed gene analysis in HeLa cells expressing high levels of phosphorylated PCNA. Differently expressed gene analysis in HeLa cells expressing high levels of phosphorylated PCNA

Cells expressing phosphorylation-mimicking PCNA, PCNA-Y211D, show elevated hallmarks specific to the epithelial-mesenchymal transition (EMT), including the upregulation of EMT-promoting factor Snail and the downregulation of EMT-inhibitory factors E-cadherin and GSK3β. These cells exhibit active cell migration and also undergo G2/M arrest. Interestingly, all of these EMT-associated activities require the activation of ATM and Akt, as inactivating these protein kinases by gene knockdown or inhibitors blocks EMT-associated signaling and cell migration. We conclude that PCNA phosphorylation promotes cancer progression via the ATM/Akt/GSK3β/Snail signaling pathway. This study, therefore, identifies a novel PCNA function and provides the molecular basis of phosphorylated PCNA-mediated cancer development and progression. Overall design: mRNA profiles PCNA phosphorylation mimic and non-phosphorylation mimic HeLa knock-in cells were generated by deep sequencing on an Illumina platform.