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

作者: Lei Qiang , Palak Shah , Mary Helen Barcellos-Hoff , Yu-Ying He

DOI: 10.1038/ONC.2015.390

关键词: Xeroderma pigmentosumTransforming growth factor betaDNA damageDDB1E2F4Cancer researchDNA repairCadherinNucleotide excision repairBiology

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

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