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The up-regulation of cysteine-rich protein 61 induced by transforming growth factor beta enhances osteosarcoma cell migration.

Abstract
Overexpressed cysteine-rich protein 61 (Cyr61) is believed to enhance osteosarcoma (OS) cell metastasis, but the mechanism of Cyr61 overexpression in OS is not clear so far. In this study 33 OS samples were analyzed by immunostaining and focused on two parts: the correlation between overexpression of Cyr61 and OS metastasis; the mechanism of regulating Cyr61 expression in OS. Twenty-five out of 33 cases (75.76 %) with metastasis showed high expression of Cyr61. Furthermore, Cyr61 expression in Saos-2 cells was reduced by siRNA, and lower expression of Cyr61 in Saos-2 cell resulted in a cell migration deficiency and had no effect on cell proliferation. Particularly, Cyr61 expression was significantly increased in Saos-2 cells in response to different dosages of transforming growth factor beta (TGF-β), indicating that the expression of Cyr61 is TGF-β dependent. A transwell assay showed that Saos-2 cells stimulated with TGF-β had a greater capacity for migration than the control cells. The p38 MAPK-specific inhibitor SB203580 was able to reduce Cyr61 expression and inhibit the migration of Saos-2 cells stimulated with TGF-β. These results obtained provide new evidence that overexpressed Cyr61 plays a key role in the metastasis of OS cells and Cyr61 is a potential target downstream of TGF-β/p38 MAPK to regulate cell migration.
AuthorsJun Chen, Yang Song, Jing Yang, Li Gong, Peng Zhao, Yong Zhang, Haichuan Su
JournalMolecular and cellular biochemistry (Mol Cell Biochem) Vol. 384 Issue 1-2 Pg. 269-77 (Dec 2013) ISSN: 1573-4919 [Electronic] Netherlands
PMID24037310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CCN1 protein, human
  • Cysteine-Rich Protein 61
  • Enzyme Inhibitors
  • Imidazoles
  • Pyridines
  • RNA, Small Interfering
  • Transforming Growth Factor beta
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580
Topics
  • Adolescent
  • Adult
  • Bone Neoplasms (genetics, metabolism, pathology)
  • Cell Line, Tumor
  • Cell Movement
  • Child
  • Cysteine-Rich Protein 61 (biosynthesis, metabolism)
  • Enzyme Inhibitors (pharmacology)
  • Female
  • Humans
  • Imidazoles (pharmacology)
  • Male
  • Neoplasm Metastasis (pathology)
  • Osteosarcoma (genetics, metabolism, pathology)
  • Pyridines (pharmacology)
  • RNA Interference
  • RNA, Small Interfering
  • Signal Transduction
  • Transforming Growth Factor beta (metabolism)
  • Up-Regulation
  • Young Adult
  • p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)

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