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Research Article Open access CC BY 4.0

The E1 Copper Binding Domain of Full-Length Amyloid Precursor Protein Promotes Epithelial to Mesenchymal Transition in DU145 Cells in an Isoform-Specific Manner

Mallory Gough, Craig Delury, Edward Parkin

International Journal of Biochemistry Research & Review · pp. 1–10 · Published 19 Dec 2014

10.9734/IJBCRR/2015/14873

Abstract

The E1 Copper Binding Domain of Full-Length Amyloid Precursor Protein Promotes Epithelial to Mesenchymal Transition in DU145 Cells in an Isoform-Specific Manner Epithelial to mesenchymal transition (EMT) confers migratory and dynamic properties on cells and, as such, plays a pivotal role in the development of metastatic, castration resistant prostate cancer. The amyloid precursor protein (APP), although most closely associated with the neurodegenerative condition Alzheimer's disease, has also been linked to the pathogenesis and prognosis of several cancers including prostate cancer. Aims: To investigate whether over-expression of APP could promote EMT in prostate cancer (PCa) DU145 cells and to determine the molecular prerequisites for this effect. Methodology: A range of APP molecular constructs were stably expressed in DU145 cells and their effects on EMT were monitored by morphological analysis and by immunoblotting for the EMT marker proteins, E-cadherin and vimentin. Results: Our results show that the full-length 695 amino acid isoform (APP695), but not APP751 or APP770, promoted EMT via a mechanism requiring an intact extracellular E1 copper binding domain and tyrosine687 within the cytosolic domain of the protein. Conclusion: Targeting the expression of APP695 or the E1 copper binding domain of the protein may, therefore, contribute to therapeutic strategies for the delay or prevention of prostate cancer metastasis.

Prostate cancer epithelial to mesenchymal transition metastasis amyloid precursor protein

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Cited by 4

Copper homeostasis as target of both consolidated and innovative strategies of anti-tumor therapy

Anastasia De Luca, Anna Barile, Mario Arciello · Journal of Trace Elements in Medicine and Biology · 2019

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