title: Inhibition of cellular growth and migration by suppression of endothelial protein C receptor (EPCR) in lung carcinoma cells.
abstract: Increasing evidence shows that beyond its role in coagulation, thrombosis interferes with carcinogenesis. Endothelial cell protein C receptor (EPCR) is a cellular receptor for protein C and activated protein C (APC). Such EPCR-induced signal transduction promotes cancer cell migration, invasion, and angiogenesis and inhibits cancer cell apoptosis. However, its role in lung carcinoma biology is yet to be demonstrated. Here, the recombinant EPCR siRNA plasmids were constructed to investigate the effects of inhibition of EPCR on human lung cancer H1299. EPCR siRNA led to inhibition of endogenous EPCR mRNA and protein expression as determined by RT-PCR and Western blotting analysis. EPCR siRNA significantly inhibited cell growth, blocked entry into the S phase of the cell cycle, and reduced the migration of H1299 cells. EPCR siRNA also decreases MMP-2 and cyclin E expression in H1299 cells. In addition, siRNA targeting of EPCR inhibited the growth of H1299 cells and decreased MVD in SCID mice tumor models. Taken together, EPCR was involved in regulating progression of human lung cancer cells. Manipulation of EPCR expression may be a potential therapeutic strategy for lung cancer.
authors.affiliation: Respiratory Department, First Affiliated Hospital of Soochow University, Suzhou, China. hwsdfyy@sohu.com
authors.forename: Wei
authors.initials: W
authors.lastname: Heng
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Huang
authors.forename: Zhao-Yue
authors.initials: ZY
authors.lastname: Wang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019927:Cyclin E / Q000378:metabolism; D000074283:Endothelial Protein C Receptor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D019927:Cyclin E; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D020778:Matrix Metalloproteinase 2