Skip to main content

Advertisement

Log in

The impact of EPLINα (Epithelial protein lost in neoplasm) on endothelial cells, angiogenesis and tumorigenesis

  • Original Paper
  • Published:
Angiogenesis Aims and scope Submit manuscript

Abstract

Background

EPLIN (epithelial protein lost in neoplasm) is a cytoskeletal associated protein involved in the regulation of actin dynamics and subsequently in cell motility. EPLIN expression is frequently reduced in a variety of cancer cells and tissues and this loss may account for increased invasive traits in cancer cells. The current study aimed to assess the role of EPLIN in endothelial cells and the angiogenic process.

Methods

EPLINα expression was enhanced in HECV endothelial cells through transfection with a pEF6 expression plasmid containing the full coding sequence of EPLINα. The impact of EPLINα on HECV cells was then assessed using a range of in vitro and in vivo models.

Results

Transfection and over-expression of HECV cells with EPLINα expression plasmid resulted in a significant reduction in cell-matrix adhesion (P = 0.003), the rate of migration (P = 0.009) and tubule formation (P = 0.007) and also enhanced paxillin staining compared to transfection controls. Additionally, MDA-MB-231 breast cancer cells co-injected with HECVEPLIN exp cells developed at a slower rate than those co-injected with HECVpEF6 cells (day 26, P = 0.05; day 33, P = 0.065, overall deviation over time P < 0.001). Treatment of HECVEPLIN exp cells with ERK inhibitor could rescue HECV cells from the inhibitory effect of EPLINα over-expression on tubule formation, returning these cells to control levels.

Conclusions

EPLINα over-expression can regulate HECV cell motility, matrix adhesion and tubule formation in vitro and slow in vivo tumour formation, suggesting an anti-angiogenic role for EPLINα. Extracellular signal-regulated kinase (ERK) also appears to be linked to the ability of EPLINα to inhibit tubule formation in vitro.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Chang DD, Park NH, Denny CT, Nelson SF, Pe M (1998) Characterization of transformation related genes in oral cancer cells. Oncogene 16(15):1921–1930

    Article  CAS  PubMed  Google Scholar 

  2. Maul RS, Chang DD (1999) EPLIN, epithelail protein lost in neoplasm. Oncogene 18:7838–7841

    Article  CAS  PubMed  Google Scholar 

  3. Chen S, Maul RS, Kim HR, Chang DD (2000) Characterization of the human EPLIN (Epithelial Protein Lost in Neoplasm) gene reveals distinct promoters for the two EPLIN isoforms. Gene 248:69–76

    Article  CAS  PubMed  Google Scholar 

  4. Jiang WG, Martin TA, Lewis-Russell JM, Douglas-Jones A, Ye L, Mansel RE (2008) Eplin-alpha expression in human breast cancer, the impact on cellular migration and clinical outcome. Mol Cancer 7:71–80

    Article  PubMed  Google Scholar 

  5. Song Y, Maul RS, Gerbin CS, Chang DD (2002) Inhibition of anchorage-independent growth of transformed NIH3T3 cells by epithelial protein lost in neoplasm (EPLIN) requires localization of EPLIN to actin cytoskeleton. Mol Biol Cell 13:1408–1416

    Article  CAS  PubMed  Google Scholar 

  6. Maul RS, Song Y, Amann KJ, Gerbin SC, Pollard TD, Chang DD (2003) EPLIN regulates actin dynamics by cross-linking and stabilizing filaments. J Cell Biol 160:399–407

    Article  CAS  PubMed  Google Scholar 

  7. Abe K, Takeichi M (2008) EPLIN mediates linkage of the cadherin-catenin complex to F-actin and stabilizes the circumferential actin belt. PNAS 105:13–19

    Article  CAS  PubMed  Google Scholar 

  8. Chircop M, Oakes V, Graham ME, Ma MP, Smith CM, Robinson PJ, Khanna KK (2009) The actin-binding and bundling protein, EPLIN, is required for cytokinesis. Cell Cycle 8(5):757–764

    CAS  PubMed  Google Scholar 

  9. Parr C, Sanders AJ, Davies G, Martin T, Lane J, Mason MD, Mansel RE, Jiang WG (2007) Matriptase-2 inhibits breast growth and invasion and correlates with favorable prognosis for breast cancer patients. Clin Cancer Res 13:3568–3576

    Article  CAS  PubMed  Google Scholar 

  10. Parr C, Watkins G, Mansel RE, Jiang WG (2004) The hepatocyte growth factor regulatory factors in human breast cancer. Clin Cancer Res 10:202–211

    Article  CAS  PubMed  Google Scholar 

  11. Jiang WG, Hiscox S, Hallett MB, Horrobin DF, Scott C, Puntis MCA (1995) Inhibition of invasion and motility of human colon cancer cells by gamma linolenic acid. Br J Cancer 71:744–752

    CAS  PubMed  Google Scholar 

  12. Jiang WG, Hiscox SE, Parr C, Martin TA, Matsumoto K, Nakamura T, Mansel RE (1999) Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells. Cancer Res 5:3695–3703

    CAS  Google Scholar 

  13. Grant DS, Tashiro K, Segui-Real B, Yamada Y, Martin GR, Kleinman HK (1989) Two different laminin domains mediate the differentiation of human endothelial cells into capillary-like structures in vitro. Cell 58:933–943

    Article  CAS  PubMed  Google Scholar 

  14. Maul RS, Gerbin CS, Chang DD (2001) Characterization of mouse epithelial protein lost in neoplasm (EPLIN) and comparison of mammalian and zebrafish EPLIN. Gene 262:155–160

    Article  CAS  PubMed  Google Scholar 

  15. Han MY, Kosako H, Watanabe T, Hattori S (2007) Extracellular signal-regulated kinase/mitogen-activated protein kinase regulates actin organization and cell motility by phosphorylating the actin cross-linking protein EPLIN. Mol Cell Biol 27(23):8190–8204

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Cancer Research Wales for their support and funding this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrew J. Sanders.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sanders, A.J., Ye, L., Mason, M.D. et al. The impact of EPLINα (Epithelial protein lost in neoplasm) on endothelial cells, angiogenesis and tumorigenesis. Angiogenesis 13, 317–326 (2010). https://doi.org/10.1007/s10456-010-9188-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10456-010-9188-7

Keywords

Navigation