Fig. 8

Mechanism of p-ERK1/2 inhibition on cancer–stromal interaction. In PDAC progression, interaction between cancer cells and stromal cells is a key regulator of ERK1/2 activation, during which cancer cells transform to an ERK1/2 activation phenotype and exhibit EMT transition tendency, and PSCs turn activated from their quiescent status. Thus enhancement of cancer–stromal interactions result in greater metastatic capacity; Whereas SCH772984 suppressed EMT transition of cancer cells, and upregulated senescence markers p15 and p16, malignancy-related genes MMP2, MMP3 and IL-6, and fibrosis markers α-SMA and Collagen Type I in PSCs. Also, its combination with an autophagy inhibitor, chloroquine, suppresses SCH772984-induced autophagy. Therefore, the combination therapy possibly leads to strong induction of cellular senescence in PSCs. In summary, dual treatment with ERK inhibitor and CQ inhibit cancer–stromal interaction and metastatic capacity