E-Cadherin–Mediated Cell Contact Controls the Epidermal Damage Response in Radiation Dermatitis

Guojiang Xie, Xiulan Ao, Tianmiao Lin, Guixuan Zhou, Ming Wang, Hanwei Wang, Yuangui Chen, Xiaobo Li, Benhua Xu, Wangzhong He, Hao Han, Yuval Ramot, Ralf Paus, Zhicao Yue

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Radiotherapy is a primary oncological treatment modality that also damages normal tissue, including the skin, and causes radiation dermatitis (RD). Here, we explore the mechanism of acute epidermal damage in radiation dermatitis. Two distinctive phases in the damage response were identified: an early destructive phase, where a burst of reactive oxygen species induces loss of E-cadherin–mediated cell contact, followed by a regenerative phase, during which Wnt and Hippo signaling are activated. A blocking peptide, as well as a neutralizing antibody to E-cadherin, works synergistically with ionizing radiation to promote the epidermal damage. In addition, ROS disassembles adherens junctions in epithelial cells via posttranslational mechanisms, that is, activation of Src/Abl kinases and degradation of β-catenin/E-cadherin. The key role of tyrosine kinases in this process is further substantiated by the rescue effect of the tyrosine kinase inhibitor genistein, and the more specific Src/Abl kinase inhibitor dasatinib: both reduced ROS-induced degradation of β-catenin/E-cadherin in vitro and ameliorated skin damage in rodent models. Finally, we confirm that the same key molecular events are also seen in human radiation dermatitis. Therefore, we propose that loss of cell contact in epidermal keratinocytes through reactive oxygen species-mediated disassembly of adherens junctions is pivotal for the acute epidermal damage in radiation dermatitis.

Original languageEnglish (US)
Pages (from-to)1731-1739
Number of pages9
JournalJournal of Investigative Dermatology
Volume137
Issue number8
DOIs
StatePublished - Aug 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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  • Cite this

    Xie, G., Ao, X., Lin, T., Zhou, G., Wang, M., Wang, H., Chen, Y., Li, X., Xu, B., He, W., Han, H., Ramot, Y., Paus, R., & Yue, Z. (2017). E-Cadherin–Mediated Cell Contact Controls the Epidermal Damage Response in Radiation Dermatitis. Journal of Investigative Dermatology, 137(8), 1731-1739. https://doi.org/10.1016/j.jid.2017.03.036