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Article

P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes

  • Authors:
    • Desseree Lysne
    • James Johns
    • Andrew Walker
    • Rachel Ecker
    • Christopher Fowler
    • Kathryn R. Lawson
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, Midwestern University, Glendale, AZ 85308, USA
  • Pages: 2541-2548
    |
    Published online on: October 14, 2014
       https://doi.org/10.3892/or.2014.3545
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Abstract

Oral and oropharyngeal cancer together constitute the sixth most common cancer worldwide, with over 400,000 new cases diagnosed each year. Early detection is paramount, as the 5-year survival rate for these cancers decreases markedly once tumors have become regionally invasive. In many tissues, including oral epithelia, neoplastic progression is accompanied by alterations in expression of the epithelial cell adhesion molecules E-cadherin and P-cadherin. Oral epithelia is one of only a few tissues in which P-cadherin levels have been noted to increase in dysplasia and well-differentiated carcinomas and decrease in advanced malignancies. In the present study, P-cadherin was overexpressed in both dysplastic and malignant oral keratinocytes to characterize the mechanisms by which aberrantly expressed P-cadherin may modulate tumor progression. We found that P-cadherin was able to potentiate ligand-dependent signaling of insulin-like growth factor 1 receptor (IGF-1R) in malignant keratinocytes and epidermal growth factor receptor (EGFR) in dysplastic cells. P-cadherin prolonged activation of the mitogen-activated protein kinase (MAPK) in both cell lines and also increased the magnitude of AKT phosphorylation in dysplastic cells. P-cadherin overexpression alone was sufficient to increase steady-state levels of the mesenchymal transcription factor Snail, increase cell motility and also induce morphological changes in dysplastic keratinocytes. Taken together, these data suggest that the aberrantly elevated levels of P-cadherin which occur in early oral tumor development may play a critical role in the augmentation of neoplastic signaling networks and in the further acquisition of aggressive phenotypes.
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Copy and paste a formatted citation
Spandidos Publications style
Lysne D, Johns J, Walker A, Ecker R, Fowler C and Lawson KR: P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes. Oncol Rep 32: 2541-2548, 2014.
APA
Lysne, D., Johns, J., Walker, A., Ecker, R., Fowler, C., & Lawson, K.R. (2014). P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes. Oncology Reports, 32, 2541-2548. https://doi.org/10.3892/or.2014.3545
MLA
Lysne, D., Johns, J., Walker, A., Ecker, R., Fowler, C., Lawson, K. R."P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes". Oncology Reports 32.6 (2014): 2541-2548.
Chicago
Lysne, D., Johns, J., Walker, A., Ecker, R., Fowler, C., Lawson, K. R."P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes". Oncology Reports 32, no. 6 (2014): 2541-2548. https://doi.org/10.3892/or.2014.3545
Copy and paste a formatted citation
x
Spandidos Publications style
Lysne D, Johns J, Walker A, Ecker R, Fowler C and Lawson KR: P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes. Oncol Rep 32: 2541-2548, 2014.
APA
Lysne, D., Johns, J., Walker, A., Ecker, R., Fowler, C., & Lawson, K.R. (2014). P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes. Oncology Reports, 32, 2541-2548. https://doi.org/10.3892/or.2014.3545
MLA
Lysne, D., Johns, J., Walker, A., Ecker, R., Fowler, C., Lawson, K. R."P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes". Oncology Reports 32.6 (2014): 2541-2548.
Chicago
Lysne, D., Johns, J., Walker, A., Ecker, R., Fowler, C., Lawson, K. R."P-cadherin potentiates ligand-dependent EGFR and IGF-1R signaling in dysplastic and malignant oral keratinocytes". Oncology Reports 32, no. 6 (2014): 2541-2548. https://doi.org/10.3892/or.2014.3545
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