Clustering of monosialyl-Gb5 initiates downstream signalling events leading to invasion of MCF-7 breast cancer cells.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Van Slambrouck S;Van Slambrouck S; Steelant WF
  • Source:
    The Biochemical journal [Biochem J] 2007 Feb 01; Vol. 401 (3), pp. 689-99.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Published by Portland Press on behalf of the Biochemical Society Country of Publication: England NLM ID: 2984726R Publication Model: Print Cited Medium: Internet ISSN: 1470-8728 (Electronic) Linking ISSN: 02646021 NLM ISO Abbreviation: Biochem J Subsets: MEDLINE
    • Publication Information:
      Original Publication: London, UK : Published by Portland Press on behalf of the Biochemical Society
    • Subject Terms:
      Signal Transduction*; Breast Neoplasms/*metabolism ; Breast Neoplasms/*pathology ; Glycosphingolipids/*metabolism ; Membrane Microdomains/*chemistry ; Membrane Microdomains/*metabolism; Cell Line, Tumor ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Focal Adhesion Kinase 1/metabolism ; Gene Expression Regulation, Neoplastic ; Glycosphingolipids/chemistry ; Humans ; Integrins/metabolism ; Matrix Metalloproteinases/metabolism ; Neoplasm Invasiveness ; Phosphatidylcholines/pharmacology ; Phospholipid Ethers
    • Abstract:
      Invasion is a complex process controlled by secretion and activation of proteases, alteration of integrin levels and GSL (glycosphingolipid) patterns. Differential organization of GSLs with specific membrane proteins and signal transducers in GEMs (GSL-enriched microdomains), initiates signalling events to modify cellular phenotype. Although the GSL monosialyl-Gb5 has been linked with invasion, its functional role in invasion is poorly described and understood. To investigate this problem, we induced the invasion of human breast cancer cells and subsequently explored the underlying mechanism. In the present study, the invasion of human MCF-7 breast cancer cells is highly dependent on clustering of monosialyl-Gb5, and the subsequent activation of monosialyl-Gb5-associated focal adhesion kinase and cSrc in GEM leading to the downstream activation of extracellular-signal-regulated kinase (ERK). As a result, we observed increased expression levels and activity of matrix metalloproteinases-2 and -9, which correlated with decreased expression of integrins alpha1 and beta1. Together these results suggest that the organization of crucial molecules in GEMs of MCF-7 cells is critical for their invasive properties.
    • References:
      FEBS Lett. 2002 Oct 30;531(1):88-92. (PMID: 12401209)
      Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10231-3. (PMID: 12149519)
      EMBO J. 2002 Dec 2;21(23):6289-302. (PMID: 12456636)
      J Cell Biol. 2003 Mar 3;160(5):753-67. (PMID: 12615911)
      Physiol Rev. 2003 Apr;83(2):337-76. (PMID: 12663862)
      J Biol Chem. 2003 Jul 18;278(29):26474-9. (PMID: 12716912)
      Adv Exp Med Biol. 2001;491:587-630. (PMID: 14533823)
      Oncogene. 2004 Sep 23;23(44):7406-15. (PMID: 15273716)
      J Lipid Res. 1971 Mar;12(2):257-9. (PMID: 4324310)
      EMBO J. 1983;2(12):2355-61. (PMID: 6141938)
      Prostate. 1988;12(1):99-110. (PMID: 3126493)
      Cancer Res. 1990 Oct 1;50(19):6184-91. (PMID: 2169338)
      Br J Cancer. 1991 Jun;63(6):867-72. (PMID: 1648947)
      Int J Cancer. 1991 Sep 30;49(3):329-34. (PMID: 1917130)
      J Biol Chem. 1994 Feb 25;269(8):5644-52. (PMID: 7509790)
      Nature. 1994 Dec 22-29;372(6508):786-91. (PMID: 7997267)
      Surgery. 1995 Jan;117(1):102-8. (PMID: 7809822)
      J Cell Biol. 1995 Sep;130(5):1181-7. (PMID: 7657702)
      Biochem Biophys Res Commun. 1997 Jul 9;236(1):218-22. (PMID: 9223455)
      Glycoconj J. 1997 Aug;14(5):569-76. (PMID: 9298689)
      Jpn J Cancer Res. 1997 Jul;88(7):652-9. (PMID: 9310138)
      J Biol Chem. 1998 Apr 10;273(15):9130-8. (PMID: 9535903)
      Mol Cell Biol. 1998 May;18(5):2571-85. (PMID: 9566877)
      Breast Cancer Res Treat. 1998 Mar;48(2):149-57. (PMID: 9596486)
      Ann N Y Acad Sci. 1998 Jun 19;845:1-10. (PMID: 9668338)
      Acta Anat (Basel). 1998;161(1-4):79-90. (PMID: 9780352)
      J Biol Chem. 1998 Dec 11;273(50):33766-73. (PMID: 9837965)
      Cancer Res. 2005 Feb 15;65(4):1335-42. (PMID: 15735019)
      J Biol Chem. 2005 Apr 22;280(16):16227-34. (PMID: 15710618)
      Mol Cancer Res. 2005 Jun;3(6):307-15. (PMID: 15972849)
      Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11041-6. (PMID: 16040804)
      J Biol Chem. 2005 Oct 21;280(42):35545-53. (PMID: 16103120)
      J Biol Chem. 2006 Jun 30;281(26):18145-55. (PMID: 16636068)
      Nat Rev Cancer. 2002 Feb;2(2):91-100. (PMID: 12635172)
      Exp Cell Res. 2000 Jan 10;254(1):180-8. (PMID: 10623478)
      Int J Oncol. 2000 Mar;16(3):529-36. (PMID: 10675485)
      Mol Med Today. 2000 Apr;6(4):149-56. (PMID: 10740253)
      Cancer Res. 2000 May 1;60(9):2361-4. (PMID: 10811109)
      Int J Cancer. 2001 May 15;92(4):527-36. (PMID: 11304687)
      J Biol Chem. 2001 May 18;276(20):16695-703. (PMID: 11278988)
      Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):225-32. (PMID: 11773621)
      Glycoconj J. 2001 Jun;18(6):475-85. (PMID: 12084983)
      FEBS Lett. 2002 Oct 30;531(1):93-8. (PMID: 12401210)
    • Grant Information:
      P20 RR016480 United States RR NCRR NIH HHS; RR-16480 United States RR NCRR NIH HHS
    • Accession Number:
      0 (Glycosphingolipids)
      0 (Integrins)
      0 (Phosphatidylcholines)
      0 (Phospholipid Ethers)
      1Y6SNA8L5S (edelfosine)
      EC 2.7.10.2 (Focal Adhesion Kinase 1)
      EC 2.7.10.2 (PTK2 protein, human)
      EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
      EC 3.4.24.- (Matrix Metalloproteinases)
    • Publication Date:
      Date Created: 20060926 Date Completed: 20070209 Latest Revision: 20181113
    • Publication Date:
      20231215
    • Accession Number:
      PMC1770852
    • Accession Number:
      10.1042/BJ20060944
    • Accession Number:
      16995838