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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: TGF-β signaling links E-cadherin loss to suppression of nucleotide excision repair.

Authors: Qiang, L; Shah, P; Barcellos-Hoff, M H; He, Y Y

Published In Oncogene, (2016 Jun 23)

Abstract: E-cadherin is a cell adhesion molecule best known for its function in suppressing tumor progression and metastasis. Here we show that E-cadherin promotes nucleotide excision repair through positively regulating the expression of xeroderma pigmentosum complementation group C (XPC) and DNA damage-binding protein 1 (DDB1). Loss of E-cadherin activates the E2F4 and p130/107 transcription repressor complexes to suppress the transcription of both XPC and DDB1 through activating the transforming growth factor-β (TGF-β) pathway. Adding XPC or DDB1, or inhibiting the TGF-β pathway, increases the repair of ultraviolet (UV)-induced DNA damage in E-cadherin-inhibited cells. In the mouse skin and skin tumors, UVB radiation downregulates E-cadherin. In sun-associated premalignant and malignant skin neoplasia, E-cadherin is downregulated in association with reduced XPC and DDB1 levels. These findings demonstrate a crucial role of E-cadherin in efficient DNA repair of UV-induced DNA damage, identify a new link between epithelial adhesion and DNA repair and suggest a mechanistic link of early E-cadherin loss in tumor initiation.

PubMed ID: 26477308 Exiting the NIEHS site

MeSH Terms: Animals; Base Sequence; Blotting, Western; Cadherins/genetics; Cadherins/metabolism*; Cell Line; Cells, Cultured; DNA Damage; DNA Repair*; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Female; HEK293 Cells; Humans; Keratinocytes/cytology; Keratinocytes/metabolism; Mice, Hairless; Microscopy, Fluorescence; RNA Interference; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Nucleic Acid; Signal Transduction*; Transforming Growth Factor beta/metabolism*

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