title: Decoy receptor 3 suppresses FasL-induced apoptosis via ERK1/2 activation in pancreatic cancer cells.
abstract: Resistance to Fas Ligand (FasL) mediated apoptosis plays an important role in tumorigenesis. Decoy receptor 3 (DcR3) is reported to interact with FasL and is overexpressed in some malignant tumors. We sought to investigate the role of DcR3 in resistance to FasL in pancreatic cancer. We compared expression of apoptosis related genes between FasL-resistant SW1990 and FasL-sensitive Patu8988 pancreatic cell lines by microarray analysis. We explored the impact of siRNA knockdown of, or exogenous supplementation with, DcR3 on FasL-induced cell growth inhibition in pancreatic cancer cell lines and expression of proteins involved in apoptotic signaling. We assessed the level of DcR3 protein and ERK1/2 phosphorylation in tumor and non-tumor tissue samples of 66 patients with pancreatic carcinoma. RNAi knockdown of DcR3 expression in SW1990 cells reduced resistance to FasL-induced apoptosis, and supplementation of Patu8988 with rDcR3 had the opposite effect. RNAi knockdown of DcR3 in SW1990 cells elevated expression of caspase 3, 8 and 9, and reduced ERK1/2 phosphorylation (P < 0.05), but did not alter phosphorylated-Akt expression. 47 tumor tissue specimens, but only 15 matched non-tumor specimens stained for DcR3 (χ(2) = 31.1447, P < 0.001). The proliferation index of DcR3 positive specimens (14.26  ±  2.67%) was significantly higher than that of DcR3 negative specimens (43.58  ±  7.88%, P < 0.01). DcR3 expression positively correlated with p-ERK1/2 expression in pancreatic cancer tissues (r = 0.607, P < 0.001). DcR3 enhances ERK1/2 phosphorylation and opposes FasL signaling in pancreatic cancer cells.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Dechun
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Shiduo
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, The Obstetrics & Gynecology Hospital of Fudan University, Shanghai 200090, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: zhoujian20150602@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D034622:RNA Interference; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics / Q000502:physiology*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053323:Receptors, Tumor Necrosis Factor, Member 6b
keywords: Apoptosis; ERK1 and ERK2 pathway; Fas ligand; Pancreatic cancer; Serum decoy receptor 3