Abstract
Prostate cancer (PCa) is the second most leading cause of death in males. Our previous studies have demonstrated that δ-catenin plays an important role in prostate cancer progression. However, the molecular mechanism underlying the regulation of δ-catenin has not been fully explored yet. In the present study, we found that δ-catenin could induce phosphorylation of p21Waf and stabilize p21 in the cytoplasm, thus blocking its nuclear accumulation for the first time. We also found that δ-catenin could regulate the interaction between AKT and p21, leading to phosphorylation of p21 at Thr-145 residue. Finally, EGF was found to be a key factor upstream of AKT/δ-catenin/p21 for promoting proliferation and metastasis in prostate cancer. Our findings provide new insights into molecular controls of EGF and the development of potential therapeutics targeting δ-catenin to control prostate cancer progression.
Keywords:
AKT; EGF; p21Waf; prostate cancer; δ-catenin.
MeSH terms
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Active Transport, Cell Nucleus
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Binding Sites / genetics
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Catenins / metabolism*
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Cell Line, Tumor
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Cell Proliferation / physiology
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Cyclin-Dependent Kinase Inhibitor p21 / chemistry
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
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Delta Catenin
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Epidermal Growth Factor / metabolism*
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Humans
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Ligands
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Male
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Models, Biological
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Mutagenesis, Site-Directed
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Neoplasm Invasiveness / pathology
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Neoplasm Invasiveness / physiopathology
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PC-3 Cells
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Phosphorylation
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / pathology*
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Protein Interaction Domains and Motifs
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Protein Stability
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Proto-Oncogene Proteins c-akt / chemistry
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Proto-Oncogene Proteins c-akt / metabolism*
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Signal Transduction
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Threonine / chemistry
Substances
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CDKN1A protein, human
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Catenins
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Cyclin-Dependent Kinase Inhibitor p21
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Ligands
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Threonine
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Epidermal Growth Factor
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Proto-Oncogene Proteins c-akt
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Delta Catenin