LIG4 mediates Wnt signalling-induced radioresistance.

Nature communications (2016-03-25)
Sohee Jun, Youn-Sang Jung, Han Na Suh, Wenqi Wang, Moon Jong Kim, Young Sun Oh, Esther M Lien, Xi Shen, Yoshihisa Matsumoto, Pierre D McCrea, Lei Li, Junjie Chen, Jae-Il Park
RÉSUMÉ

Despite the implication of Wnt signalling in radioresistance, the underlying mechanisms are unknown. Here we find that high Wnt signalling is associated with radioresistance in colorectal cancer (CRC) cells and intestinal stem cells (ISCs). We find that LIG4, a DNA ligase in DNA double-strand break repair, is a direct target of β-catenin. Wnt signalling enhances non-homologous end-joining repair in CRC, which is mediated by LIG4 transactivated by β-catenin. During radiation-induced intestinal regeneration, LIG4 mainly expressed in the crypts is conditionally upregulated in ISCs, accompanied by Wnt/β-catenin signalling activation. Importantly, among the DNA repair genes, LIG4 is highly upregulated in human CRC cells, in correlation with β-catenin hyperactivation. Furthermore, blocking LIG4 sensitizes CRC cells to radiation. Our results reveal the molecular mechanism of Wnt signalling-induced radioresistance in CRC and ISCs, and further unveils the unexpected convergence between Wnt signalling and DNA repair pathways in tumorigenesis and tissue regeneration.

MATÉRIAUX
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Marque
Description du produit

Sigma-Aldrich
iCRT14, ≥98% (HPLC)
Sigma-Aldrich
Anti-LIG4 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution

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