Methylation of , a key ERK signaling regulator, is a novel synthetic lethality marker of ATM inhibitors in human lung cancer.

The role of methylation in lung cancer and its therapeutic application remains unclear. Nine lung cancer cell lines and 123 cases of cancer tissue samples were employed. was methylated in 53.66% of primary lung cancer. Restoration of expression induced cell apoptosis and G2/M phase arrest, and inhibited colony formation, cell proliferation, migration and invasion. suppressed H1299 cell xenograft growth in mice. Methylation of activated ERK signaling and sensitized H1299 and H23 cells to AZD0156, an ATM inhibitor. The expression of is regulated by promoter region methylation. Methylation of is a potential lung cancer diagnostic marker and a novel synthetic lethal therapeutic marker for AZD0156.