title: 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.
authors.affiliation: Institute of Osteoscarcoma, Tangdu Hospital of Fourth Military Medical University, Xi'an, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haichuan
authors.initials: H
authors.lastname: Su
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002648:Child; D055515:Cysteine-Rich Protein 61 / Q000096:biosynthesis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
references.citation: Lancet. 2004 Jan 3;363(9402):62-4
references.pmid: 14723997
references.citation: EMBO J. 2007 Sep 5;26(17):3957-67
references.pmid: 17673906
references.citation: Endocr Relat Cancer. 2004 Dec;11(4):781-91
references.pmid: 15613452
references.citation: J Am Coll Surg. 2005 Mar;200(3):371-7
references.pmid: 15737847
references.citation: Int J Cancer. 2012 Dec 1;131(11):2584-95
references.pmid: 22487809
references.citation: Cancer Biol Ther. 2011 Dec 1;12(11):978-88
references.pmid: 22104964
references.citation: Eur J Biochem. 2003 Aug;270(16):3408-21
references.pmid: 12899698
references.citation: Pediatr Blood Cancer. 2011 Sep;57(3):415-22
references.pmid: 21563300
references.citation: Am J Pathol. 2010 Feb;176(2):939-51
references.pmid: 20056838
references.citation: Biochem Biophys Res Commun. 2011 Oct 14;414(1):181-5
references.pmid: 21945933
references.citation: Cancer Treat Res. 2009;152:219-37
references.pmid: 20213393
references.citation: Sarcoma. 2012;2012:704872
references.pmid: 22550423
references.citation: Expert Rev Anticancer Ther. 2006 Jul;6(7):1075-85
references.pmid: 16831079
references.citation: Angiogenesis. 2002;5(3):153-65
references.pmid: 12831056
references.citation: J Bone Miner Res. 2012 Jan;27(1):58-67
references.pmid: 21976359
references.citation: Nature. 2003 Oct 9;425(6958):577-84
references.pmid: 14534577
references.citation: J Bone Miner Res. 2011 Jul;26(7):1533-42
references.pmid: 21312266
references.citation: Cancer. 2008 Jul 15;113(2):419-25
references.pmid: 18484657
references.citation: J Biol Chem. 1999 Dec 24;274(52):37292-300
references.pmid: 10601295
references.citation: J Biol Chem. 2006 Dec 29;281(52):40412-9
references.pmid: 17085434
references.citation: Cancer Gene Ther. 2011 Jun;18(6):450-6
references.pmid: 21436869
references.citation: Cancer Lett. 2007 Feb 8;246(1-2):230-6
references.pmid: 16616811
references.citation: J Biol Chem. 2002 Oct 25;277(43):41220-9
references.pmid: 12149257
references.citation: Bone. 2006 May;38(5):671-7
references.pmid: 16311085
references.citation: Science. 2004 Feb 6;303(5659):848-51
references.pmid: 14764882
references.citation: Int J Cancer. 1994 Aug 1;58(3):440-5
references.pmid: 8050825
references.citation: Sarcoma. 2011;2011:959248
references.pmid: 21559216
references.citation: Endocr Rev. 1999 Apr;20(2):189-206
references.pmid: 10204117
references.citation: Biochem Biophys Res Commun. 2012 Aug 31;425(3):607-12
references.pmid: 22885178
references.citation: J Biol Chem. 1997 Jan 17;272(3):1429-32
references.pmid: 8999807
references.citation: Cancer Res. 2003 Nov 15;63(22):7791-8
references.pmid: 14633705
references.citation: EMBO J. 2002 Jul 15;21(14):3749-59
references.pmid: 12110587
references.citation: Clin Cancer Res. 2005 Aug 15;11(16):5809-20
references.pmid: 16115920
references.citation: Cancer Res. 2007 Sep 1;67(17):8149-55
references.pmid: 17804727
references.citation: Cancer Res. 2008 Sep 15;68(18):7323-31
references.pmid: 18794119