title: Collagen triple helix repeat containing-1 promotes pancreatic cancer progression by regulating migration and adhesion of tumor cells.
abstract: Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein involved in vascular remodeling, bone formation and developmental morphogenesis. CTHRC1 has recently been shown to be expressed in human cancers such as breast cancer and melanoma. In this study, we show that CTHRC1 is highly expressed in human pancreatic cancer tissues and plays a role in the progression and metastasis of the disease. CTHRC1 promoted primary tumor growth and metastatic spread of cancer cells to distant organs in orthotopic xenograft tumor mouse models. Overexpression of CTHRC1 in cancer cells resulted in increased motility and adhesiveness, whereas these cellular activities were diminished by down-regulation of the protein. CTHRC1 activated several key signaling molecules, including Src, focal adhesion kinase, paxillin, mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase and Rac1. Treatment with chemical inhibitors of Src, MEK or Rac1 and expression of dominant-negative Rac1 attenuated CTHRC1-induced cell migration and adhesion. Collectively, our results suggest that CTHRC1 has a role in pancreatic cancer progression and metastasis by regulating migration and adhesion activities of cancer cells.
authors.affiliation: Immunotherapy Research Center,  Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806,  South Korea.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Park
authors.forename: Seokho
authors.initials: S
authors.lastname: Kim
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Jo
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yeonsil
authors.initials: Y
authors.lastname: Hwang
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Si Young
authors.initials: SY
authors.lastname: Song
authors.forename: Dong-Ki
authors.initials: DK
authors.lastname: Lee
authors.forename: Sang Seok
authors.initials: SS
authors.lastname: Koh
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000556:secondary; D016022:Case-Control Studies; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051419:Paxillin / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C502426:CTHRC1 protein, human; D016326:Extracellular Matrix Proteins; D051419:Paxillin; C107953:RAC1 protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein