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Review
. 2012 Jun 15;72(12):2917-23.
doi: 10.1158/0008-5472.CAN-11-3498. Epub 2012 Jun 1.

Dishonorable discharge: the oncogenic roles of cleaved E-cadherin fragments

Justin M David  1 , Ayyappan K Rajasekaran
Affiliations
Review

Dishonorable discharge: the oncogenic roles of cleaved E-cadherin fragments

Justin M David et al. Cancer Res. .

Abstract

Strong cell-cell interactions represent a major barrier against cancer cell mobility, and loss of intercellular adhesion by E-cadherin is a fundamental change that occurs during the progression of cancer to invasive disease. However, some aggressive carcinomas retain characteristics of differentiated epithelial cells, including E-cadherin expression. Emerging evidence indicates that proteolysis of E-cadherin generates fragments that promote tumor growth, survival, and motility, suggesting that E-cadherin cleavage converts this tumor suppressor into an oncogenic factor. In this review we discuss the emerging roles of cleaved E-cadherin fragments as modulators of cancer progression, and explore the translational and clinical implications of this research.

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Conflict of interest statement

Conflicts of Interest: None

Figures

Figure 1
Figure 1
Generation of E-cadherin fragments and their functions. A, cleavage of the full-length E-cadherin by α-secretase, γ-secretase, and caspase-3 generates the sE-cad and E-cad/CTF1, E-cad/CTF2, and E-cad/CTF3 fragments, respectively. B, oncogenic functions of the sE-cad and E-cad/CTF2 fragments. Generation of sE-cad by E-cadherin cleavage reduces the amount of full-length E-cadherin on the plasma membrane (1), disrupts existing adherens junctions (2), activates the expression of MMPs to augment ectodomain shedding (3), and activates EGFR pathway signaling by different mechanisms (4). Intracellular cleavage of E-cadherin activates Wnt/β-catenin pathway signaling (5). CD, cytoplasmic domain; TM, transmembrane domain.
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References

    1. Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006;66(17):8319–8326. - PubMed
    1. Gumbiner BM. Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol. 2005;6(8):622–634. - PubMed
    1. Qian X, Karpova T, Sheppard AM, McNally J, Lowy DR. E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases. EMBO J. 2004;23(8):1739–1748. - PMC - PubMed
    1. Redmer T, Diecke S, Grigoryan T, Quiroga-Negreira A, Birchmeier W, Besser D. E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming. EMBO Rep. 2011;12(7):720–726. - PMC - PubMed
    1. De Wever O, Derycke L, Hendrix A, De Meerleer G, Godeau F, Depypere H, et al. Soluble cadherins as cancer biomarkers. Clin Exp Metastasis. 2007;24(8):685–697. - PubMed

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