Skip to main content

Advertisement

Log in

Endothelial cadherins in cancer

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Cadherins are cell adhesion receptors that play important roles in embryogenesis and tissue homoeostasis. Endothelial cells express various members of the cadherin superfamily, in particular vascular endothelial (VE-) cadherin, which is the main adhesion receptor of endothelial adherens junctions and neural (N-) cadherin, which is normally localized outside the junctions and may mediate adhesion between endothelial cells and non-endothelial cells. Dysregulation of cadherin expression has been implicated in tumor progression, in particular the loss of epithelial (E-) cadherin expression or function and the gain of N-cadherin. Moreover, more recently, aberrant expression of VE-cadherin was observed in certain cancer types. In breast carcinoma, VE-cadherin was shown to promote tumor cell proliferation and invasion through enhancing TGF-β signaling. Thus, in breast cancer, the cadherin switch involves another player, vascular endothelial cadherin, which is part of an intricate interplay of classical cadherins in breast cancer progression.

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

Similar content being viewed by others

References

  • Andrews JL, Kim AC, Hens JR (2012) The role and function of cadherins in the mammary gland. Breast Cancer Res 14:203

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Berx G, van Roy F (2009) Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol 1:a003129

    Article  PubMed Central  PubMed  Google Scholar 

  • Breier G, Breviario F, Caveda L, Berthier R, Schnürch H, Gotsch U, Vestweber D, Risau W, Dejana E (1996) Molecular cloning and expression of murine vascular endothelial-cadherin in early stage development of cardiovascular system. Blood 87:630–641

    PubMed  CAS  Google Scholar 

  • Breier G, Risau W (1996) The role of vascular endothelial growth factor in blood vessel formation. Trends Cell Biol 6:454–456

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oosthuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter MC, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert JM, Collen D, Dejana E (1999) Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 98:147–157

    Article  PubMed  CAS  Google Scholar 

  • Cavallaro U, Liebner S, Dejana E (2006) Endothelial cadherins and tumor angiogenesis. Exp Cell Res 312:659–667

    Article  PubMed  CAS  Google Scholar 

  • Corada M, Zanetta L, Orsenigo F, Breviario F, Lampugnani MG, Bernasconi S, Liao F, Hicklin DJ, Bohlen P, Dejana E (2002) A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability. Blood 100:905–911

    Article  PubMed  CAS  Google Scholar 

  • Dejana E (2004) Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol 5:261–270

    Article  PubMed  CAS  Google Scholar 

  • Dumont N, Wilson MB, Crawford YG, Reynolds PA, Sigaroudinia M, Tlsty TD (2008) Sustained induction of epithelial to mesenchymal transition activates DNA methylation of genes silenced in basal-like breast cancers. Proc Natl Acad Sci USA 105:14867–14872

    Article  PubMed Central  PubMed  Google Scholar 

  • Giampietro C, Taddei A, Corada M, Sarra-Ferraris GM, Alcalay M, Cavallaro U, Orsenigo F, Lampugnani MG, Dejana E (2012) Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells. Blood 119:2159–2170

    Article  PubMed  CAS  Google Scholar 

  • Giannotta M, Trani M, Dejana E (2013) VE-cadherin and endothelial adherens junctions: active guardians of vascular integrity. Dev Cell 26:441–454

    Article  PubMed  CAS  Google Scholar 

  • Gilles C, Polette M, Mestdagt M, Nawrocki-Raby B, Ruggeri P, Birembaut P, Foidart JM (2003) Transactivation of vimentin by β-catenin in human breast cancer cells. Cancer Res 63:2658–2664

    PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  PubMed  CAS  Google Scholar 

  • Hazan RB, Phillips GR, Qiao RF, Norton L, Aaronson SA (2000) Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J Cell Biol 148:779–790

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hendrix MJ, Seftor EA, Meltzer PS, Gardner LM, Hess AR, Kirschmann DA, Schatteman GC, Seftor RE (2001) Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry. Proc Natl Acad Sci USA 98:8018–8023

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hollestelle A, Peeters JK, Smid M, Timmermans M, Verhoog LC, Westenend PJ, Heine AA, Chan A, Sieuwerts AM, Wiemer EA, Klijn JG, van der Spek PJ, Foekens JA, Schutte M, den Bakker MA, Martens JW (2013) Loss of E-cadherin is not a necessity for epithelial to mesenchymal transition in human breast cancer. Breast Cancer Res Treat 138:47–57

    Article  PubMed  CAS  Google Scholar 

  • Labelle M, Schnittler HJ, Aust DE, Friedrich K, Baretton G, Vestweber D, Breier G (2008) Vascular endothelial cadherin promotes breast cancer progression via transforming growth factor β signaling. Cancer Res 68:1388–1397

    Article  PubMed  CAS  Google Scholar 

  • Liao F, Li Y, O’Connor W, Zanetta L, Bassi R, Santiago A, Overholser J, Hooper A, Mignatti P, Dejana E, Hicklin DJ, Bohlen P (2000) Monoclonal antibody to vascular endothelial-cadherin is a potent inhibitor of angiogenesis, tumor growth, and metastasis. Cancer Res 60:6805–6810

    PubMed  CAS  Google Scholar 

  • Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe’er J, Trent JM, Meltzer PS, Hendrix MJ (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739–752

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • McDonald DM, Munn L, Jain RK (2000) Vasculogenic mimicry: how convincing, how novel, and how significant? Am J Pathol 156:383–388

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Micalizzi DS, Farabaugh SM, Ford HL (2010) Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia 15:117–134

    Article  PubMed Central  PubMed  Google Scholar 

  • Nieman MT, Prudoff RS, Johnson KR, Wheelock MJ (1999) N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol 147:631–644

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Paulis YWJ, Soetekouw PM, Verheul HMW, Tjan-Heijnen VCG, Griffioen AW (2010) Signalling pathways in vasculogenic mimicry. Biochim Biophys Acta 1806:18–28

    PubMed  CAS  Google Scholar 

  • Peinado H, Olmeda D, Cano A (2007) Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7:415–428

    Article  PubMed  CAS  Google Scholar 

  • Rezaei M, Friedrich K, Wielockx B, Kuzmanov A, Kettelhake A, Labelle M, Schnittler H, Baretton G, Breier G (2012) Interplay between neural-cadherin and vascular endothelial-cadherin in breast cancer progression. Breast Cancer Res 14:R154

    Article  PubMed  CAS  Google Scholar 

  • Rudini N, Felici A, Giampietro C, Lampugnani M, Corada M, Swirsding K, Garrè M, Liebner S, Letarte M, ten Dijke P, Dejana E (2008) VE-cadherin is a critical endothelial regulator of TGF-β signalling. EMBO J 27:993–1004

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Seftor RE, Hess AR, Seftor EA, Kirschmann DA, Hardy KM, Margaryan NV, Hendrix MJ (2012) Tumor cell vasculogenic mimicry: from controversy to therapeutic promise. Am J Pathol 181:1115–1125

    Article  PubMed  CAS  Google Scholar 

  • Takeichi M (2011) Self-organization of animal tissues: cadherin-mediated processes. Dev Cell 21:24–26

    Google Scholar 

  • von Marschall Z, Cramer T, Höcker M, Burde R, Plath T, Schirner M, Heidenreich R, Breier G, Riecken EO, Wiedenmann B, Rosewicz S (2000) De novo expression of vascular endothelial growth factor in human pancreatic cancer: evidence for an autocrine mitogenic loop. Gastroenterology 119:1358–1372

    Article  Google Scholar 

  • Yamada S, Pokutta S, Drees F, Weis WI, Nelson WJ (2005) Deconstructing the cadherin-catenin-actin complex. Cell 123:889–901

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yilmaz M, Christofori G (2009) EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev 28:15–33

    Article  PubMed  Google Scholar 

  • Zanetta L, Corada M, Grazia Lampugnani M, Zanetti A, Breviario F, Moons L, Carmeliet P, Pepper MS, Dejana E (2005) Downregulation of vascular endothelial-cadherin expression is associated with an increase in vascular tumor growth and hemorrhagic complications. Thromb Haemost 93:1041–1046

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Georg Breier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Breier, G., Grosser, M. & Rezaei, M. Endothelial cadherins in cancer. Cell Tissue Res 355, 523–527 (2014). https://doi.org/10.1007/s00441-014-1851-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-014-1851-7

Keywords

Navigation