Skip to main content

Advertisement

Log in

N-acetylglucosaminyltransferase V mediates cell migration and invasion of mouse mammary tumor cells 4TO7 via RhoA and Rac1 signaling pathway

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

In tumor cells, alterations in cellular glycosylation may play a key role in their metastatic behavior. Using small interfering RNA against GnT-V, we found that the expression of GnT-V and β1,6GlcNAc branching were significantly reduced which was particularly accompanied by the arrest in both cell migration and invasion as compared to the negative control. Moreover, the suppressed GnT-V expression by siRNA technique inactivated the signaling molecules including Rac1, cofilin, Erk and Akt, and activated RhoA levels in cells lacking GnT-V, but revealed no impact on Cdc42 activity. All these notions disclose for the first time that GnT-V and β1, 6GlcNAc branching mediate the cell migration and invasion in Rac1-positive and RhoA-negative regulatory manners.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

FBS:

Fetal bovine serum

FITC:

Fluorescein isothyocianate

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

mAb:

Monoclonal antibody

HRP:

Horseradish peroxidase

PBS:

Phosphate-buffered saline

BSA:

Bovine serum albumin

TBS:

Tris-buffered saline

PHA-L:

Phaseolus vulgaris Leucoagglutinin

Fn:

Fibronectin

GnT-V:

N-acetylglucosaminyltransferase V

PI3K:

Phosphatidylinositol 3-kinase

MAPK:

Mitogen-activated protein kinase

Erk:

Extracellular signal-regulated kinase

References

  1. Helenius A, Aebi M (2004) Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem 73:1019–1049

    Article  PubMed  CAS  Google Scholar 

  2. Roseman S (2001) Reflections on glycobiology. J Biol Chem 276:41527–41542

    Article  PubMed  CAS  Google Scholar 

  3. Dennis JW, Granovsky M, Warren CE (1999) Glycoprotein glycosylation and cancer progression. Biochim Biophys Acta 1473:21–34

    PubMed  CAS  Google Scholar 

  4. Dube DH, Bertozzi CR (2005) Glycans in cancer and inflammation-potential for therapeutics and diagnostics. Nat Rev Drug Discov 4:477–488

    Article  PubMed  CAS  Google Scholar 

  5. Granovsky M, Fata J, Pawling J et al (2000) Suppression of tumor growth and metastasis in Mgat5-deficient mice. Nat Med 6:306–312

    Article  PubMed  CAS  Google Scholar 

  6. Guo HB, Lee I, Bryan BT et al (2005) Deletion of mouse embryo fibroblast N-acetylglucosaminyltransferase V stimulates alpha5beta1 integrin expression mediated by the protein kinase C signaling pathway. J Biol Chem 280:8332–8342

    Article  PubMed  CAS  Google Scholar 

  7. Murata K, Miyoshi E, Ihara S et al (2004) Attachment of human colon cancer cells to vascular endothelium is enhanced by N-acetylglucosaminyltransferase V. Oncology 66:492–501

    Article  PubMed  CAS  Google Scholar 

  8. Jaffe AB, Hall A (2005) Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21:247–269

    Article  PubMed  CAS  Google Scholar 

  9. Chan AY, Coniglio SJ, Chuang YY et al (2005) Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion. Oncogene 24:7821–7829

    Article  PubMed  CAS  Google Scholar 

  10. Sahai E, Marshall CJ (2002) RHO-GTPases and cancer. Nat Rev Cancer 2:133–142

    Article  PubMed  Google Scholar 

  11. Zhao YX, Li J, Wang JJ et al (2007) Role of cell surface oligosaccharides of mouse mammary tumor cell lines in cancer metastasis. Indian J Biochem Biophys 44:145–151

    PubMed  CAS  Google Scholar 

  12. Chodniewicz D, Klemke RL (2004) Guiding cell migration through directed extension and stabilization of pseudopodia. Exp Cell Res 301:31–37

    Article  PubMed  CAS  Google Scholar 

  13. Plastino J, Sykes C (2005) The actin slingshot. Curr Opin Cell Biol 17:62–66

    Article  PubMed  CAS  Google Scholar 

  14. Ghosh M, Song X, Mouneimne G et al (2004) Cofilin promotes actin polymerization and defines the direction of cell motility. Science 304:743–746

    Article  PubMed  CAS  Google Scholar 

  15. Wang W, Mouneimne G, Sidani M et al (2006) The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors. J Cell Biol 173:395–404

    Article  PubMed  CAS  Google Scholar 

  16. Reddy KB, Nabha SM, Atanaskova N (2003) Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev 22:395–403

    Article  PubMed  CAS  Google Scholar 

  17. Meng Q, Xia C, Fang J et al (2006) Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation through the p70S6K1 pathway. Cell Signal 18:2262–2271

    Article  PubMed  CAS  Google Scholar 

  18. Merlot S, Firtel RA (2003) Leading the way: directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J Cell Sci 116:3471–3478

    Article  PubMed  CAS  Google Scholar 

  19. Cheung P, Dennis JW (2007) Mgat5 and Pten interact to regulate cell growth and polarity. Glycobiology. 17:767–773

    Article  PubMed  CAS  Google Scholar 

  20. Burridge K, Wennerberg K (2004) Rho and Rac take center stage. Cell 116:167–179

    Article  PubMed  CAS  Google Scholar 

  21. Raftopoulou M, Hall A (2004) Cell migration: Rho GTPases lead the way. Dev Biol 265:23–32

    Article  PubMed  CAS  Google Scholar 

  22. Besson A, Gurian-West M, Schmidt A et al (2004) p27Kip1 modulates cell migration through the regulation of RhoA activation. Genes Dev 18:862–876

    Article  PubMed  CAS  Google Scholar 

  23. Vial E, Sahai E, Marshall CJ (2003) ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. Cancer Cell 4:67–79

    Article  PubMed  CAS  Google Scholar 

  24. Dawe HR, Minamide LS, Bamburg JR et al (2003) ADF/cofilin controls cell polarity during fibroblast migration. Curr Biol 13:252–257

    Article  PubMed  CAS  Google Scholar 

  25. Ridley MA, Schwartz AJ, Burridge K et al (2003) Cell migration: integrating signals from front to back. Science 302:1704–1709

    Article  PubMed  CAS  Google Scholar 

  26. Katoh H, Hiramoto K, Negishi M (2006) Activation of Rac1 by RhoG regulates cell migration. J Cell Sci 119:56–65

    Article  PubMed  CAS  Google Scholar 

  27. Steffen A, Rottner K, Ehinger J et al (2004) Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. EMBO J 23:749–759

    Article  PubMed  CAS  Google Scholar 

  28. Czuchra A, Wu X, Meyer H et al (2005) Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells. Mol Cell Biol 16:4473–4484

    Article  CAS  Google Scholar 

Download references

Acknowledgment

This research was supported by the National Basic Research Program Grant (973) (2003CB716400).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Meiyu Geng.

Additional information

Yunxue Zhao and Jing Li contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, Y., Li, J., Xing, Y. et al. N-acetylglucosaminyltransferase V mediates cell migration and invasion of mouse mammary tumor cells 4TO7 via RhoA and Rac1 signaling pathway . Mol Cell Biochem 309, 199–208 (2008). https://doi.org/10.1007/s11010-007-9656-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9656-6

Keywords

Navigation