Knockdown of PPP2R2B inhibits pancreatic cancer progression via the ERK/MAPK pathway by modulating EMT and apoptosis

Pancreatic cancer (PC) is one of the most lethal types of cancer, as current treatments are largely ineffective. Our research uncovers that PPP2R2B is overexpressed in a majority of PC cases, playing a significant role in the growth and spread of PC tumors. Knockdown of PPP2R2B inhibits PC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while promoting cell apoptosis. Conversely, overexpression of PPP2R2B enhances these processes, leading to increased proliferation, migration, invasion, and EMT, and reduced apoptosis. Further analysis showed that reducing PPP2R2B levels in PC inactivates the MAPK pathways—ERK, JNK, and p38, ultimately promoting PC growth. The addition of an ERK inhibitor reverses the effects of PPP2R2B knockdown, restoring cell proliferation, migration, and invasion. Our experiments in live subjects demonstrate that removing PPP2R2B inhibits tumor growth in PC mouse models and alters the levels of proteins involved in EMT and cell death. These findings demonstrate that PPP2R2B contributes to PC progression by modulating EMT and apoptosis through the ERK/MAPK pathway. Targeting PPP2R2B or its downstream signaling pathways may offer a promising therapeutic strategy for pancreatic cancer.