Fig. 1

PKCδ is a key mediator of EGFR downstream signaling and closely associates with tumor non-inflamed phenotype. A Protein expression was comprehensively compared among normal tissue, wild-type, and mutated EGFR cancer. 7219 and 6779 significant proteins found in mutation and non-mutation groups respectively. B 262 proteins were found to be related to EGFR proteins, including 20 kinase proteins and 7 immune regulating proteins. C In phosphoproteomic analysis, 10 phosphosites of 8 proteins from these 262 EGFR related proteins were significantly regulated in EGFR mutation tumor. D In NSCLC, phosphorylation of PKCδ was directly related to EGFR active mutation. E Treatment of EGFR TKI suppressed the phosphorylation of PKCδ in H1975 cells. F Compared with non-EGFR mutated A549 cells, H1975 cells were more sensitive to the treatment of PKCδ inhibitor rottlerin. G Each PKC isoform contains 3–30 phosphorylation sites respectively and exhibits different profiling in lung cancer. The phosphorylation of PKCδ was most frequently correlated: more than 75% of its phosphorylation site was relatively increased