Fig. 5.

H3K9 methyltransferases and demethylases control lung tumor-propagating cells through transcriptional regulation of Mmp10, KRAS and ECM genes. In lung adenocarcinoma non-stem tumor cells, G9a is relatively highly expressed and H3K9me2 KDMs are relatively under-expressed. Chromatin is relatively enriched in H3K9me2, which represses the transcription of Sca-1, Mmp10, and other genes associated with mutant KRAS and ECM regulation. Loss of G9a or gain of H3K9me2 KDMs reduces H3K9me2 and allows for the expression of previously repressed genes. This enables tumor cells to acquire the tumor-propagating cell phenotype, and the expansion of the tumor-propagating cell population drives lung adenocarcinoma progression and metastasis. Re-expression of G9a or antagonism of H3K9me2 KDMs can reverse the TPC phenotypes, mitigating lung adenocarcinoma progression