Figure 3 from The Lysine Demethylase KDM4C Is an Oncogenic Driver and Regulates ERK Activity in KRAS-Mutant Pancreatic Ductal Adenocarcinoma

KDM4C expression correlates with ERK activity. A, Top enriched IPA pathways from RNA-seq data from KDM4C KO vs. WT AsPC1 are cell-cycle arrest, inhibition of MEK/ERK, protein synthesis inhibition, and increased oxidative phosphorylation and apoptosis, whereas ATF4, MYC, and ERK1/2 are among the top downregulated networks. B, GSEA plot from RNA-seq data showing downregulated KRAS and MYC signatures in KDM4C-depleted cells. C, RPPA data demonstrate downregulation of the ERK pathway in two different KDM4C-null clones. D, Western blot validating downregulation of ERK phosphorylation in human PDAC cell line AsPC1 and in mouse PDAC cell line (KPC-mT4) KDM4C KO clones. E, Representative micrographs of pERK expression by IHC in PDAC tumors harvested at day 30 from mice injected with PDAC cell line KPC-mT4 demonstrates downregulation of pERK in the KDM4C KO clones compared with untreated KPC-mT4 (Scale bar, 100 μm).