Fig. 4

p38α MAPK mediated regulation of LY6G6D. A Upper panel, a network analysis reveals a putative role of TNF-α (blue) and p38α MAPK (red) in the regulation of LY6G6D. Down left, Heatmap of candidates LY6G6D regulatory proteins in mucinous and classical adenocarcinoma from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Down right, MAPK14 expression in normal, mucinous and non-mucinous CRC. The p values are from t test Welch-corrected. B Left panel, Heatmap of CRC transcriptomic changes for the candidate genes in mucinous and adenocarcinoma from TCGA dataset. Right, the table shows significant co-modification of p38α MAPK (MAPK14) and LY6G6D (yellow). C Left panel, western blot analysis of LY6G6D and p38α MAPK protein normalized to β-actin in control (CC) transfected with empty vector or p38α MAPK knock-down (shp38α) HCT116 cells. Right panels, densitometry analysis normalized to β-actin and, expressed as mean and standard deviation (SD) performed on triplicate experiments. *p < 0.05, **p < 0.01. D Upper panels, western blot analysis of P-ERK1/2, LY6G6D and p38α normalized to β-actin in extracts from the HCT116 control or p38α knock-down treated with the MEK inhibitor, trametinib, or untreated (−). Lower panel, histograms show the mean and SD performed on triplicate blots and normalized to β-actin for LY6G6D levels. *p < 0.05, **p < 0.01