Dying tumor cells stimulate proliferation of living tumor cells via caspase‐dependent protein kinase Cδ activation in pancreatic ductal adenocarcinoma

• DOI: 10.1016/j.molonc.2014.07.024
• Publication Date: 2014-08-07T13:18:55Z
• Authors: Jin Cheng; Ling Tian; Jingjing Ma; Yanping Gong; Zhengxiang Zhang; Zhiwei Chen; Bing Xu; Hui Xiong; Chuanyuan Li; Qian Huang
• Keywords: Pancreatic tumor

Pancreatic cancer is one of the most lethal human cancers, and radiotherapy often implemented for locally advanced pancreatic ductal adenocarcinoma. Tumor cell repopulation a major challenge in treating cancers after radiotherapy. In order to address problem tumor repopulation, our previous studies have demonstrated that dying cells stimulate proliferation living particular, undergoing apoptosis also activate survival or signals release growth factors surrounding cells. present study, we used an vitro model examine possible mechanisms stimulated cancer. this model, small number living, luciferase‐labeled (reporter) were seeded onto layer much larger irradiated, unlabeled was measured over time as gage repopulation. Our results indicate Panc1 feeder significantly reporter Importantly, identified percentage apoptotic cleavage caspases 3 7 protein kinase Cδ (PKCδ) increased irradiated We presumed PKCδ integral mediators process stimulation growth. demonstrate importance 3, PKCδ, introduced dominant‐negative mutants caspase (DN_C3), (DN_C7), (DN_PKCδ) into using lentiviral vectors. The stably transduced feeders found significant decrease when compared with wild‐type feeders. Moreover, role further confirmed pan PKC inhibitor GF109203x specific inhibitor, rottlerin. Additionally, phosphorylation Akt, p38 mitogen‐activated (MAPK) c‐Jun N‐terminal kinase/stress‐activated (JNK1/2) Mechanistically, attenuated both DN_C3 DN_C7 cells, Akt MAPK DN_PKCδ following radiation. Thus, report suggests novel finding cellular signaling 3/7‐PKCδ‐Akt/p38 crucial