H3K9 methyltransferases and demethylases control lung tumor-propagating cells and lung cancer progression (experiment 2)

We have identified the histone methyltransferases G9a/Glp as suppressors of aggressive lung tumor-propagating cells (TPCs). Chemically inhibiting G9a/Glp promoted TPC phenotypes in lung adenocarcinoma cells, and caused chromatin changes at genes associated with the differentiation of stem cells. G9a/Glp inhibition in lung progenitor cell organoid cultures disrupted alveolar differentiation. Depleting G9a during tumorigenesis enriched for TPCs, accelerating disease progression and metastasis. Demethylase inhibition decreased lung adenocarcinoma progression in vivo. Genome-wide maps of histone H3K27 acetylation and H3K9 dimethylation in CK1750 cells treated with either DMSO or a G9a/GLP inhibitor, UNC0638.