Effect of β-catenin silencing in overcoming radioresistance of head and neck cancer cells by antagonizing the effects of AMPK on Ku70/Ku80.

Effect of β-catenin silencing in overcoming radioresistance of head and neck cancer cells by antagonizing the effects of AMPK on Ku70/Ku80.

Head Neck. 2015 Dec 29;

Authors: Chang HW, Nam HY, Kim HJ, Moon SY, Kim MR, Lee M, Kim GC, Kim SW, Kim SY

Abstract
BACKGROUND: We attempted to elucidate the mechanism of cell death after radiation by studying how β-catenin silencing controls the radiation sensitivity of radioresistant head and neck cancer cells.
METHODS: The most radioresistant cancer cell line (AMC-HN-9) was selected for study. Targeted silencing of β-catenin was used on siRNAs. Sensitivity to radiation was examined using clonogenic and methylthiazol tetrazolium (MTT) assays.
RESULTS: A combination of irradiation plus β-catenin silencing led to a significant reduction in the inherent radioresistance of AMC-HN-9 cells. Although expression of Ku70/80 was upregulated in AMC-HN-9 cells after irradiation, Ku70/80 was dramatically decreased in a combination of irradiation and β-catenin silencing. Interestingly, irradiation-induced Ku70/80 was completely prevented by β-catenin silencing-induced LKB1/AMP-activated protein kinase (LKB1/AMPK) signal.
CONCLUSION: The LKB1/AMPK pathway might relay the signal between the Wnt/β-catenin pathway and the Ku70/Ku80 DNA repair machinery, and play a decisive role in fine-tuning the responses of cancer cells to irradiation. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.

PMID: 26713771 [PubMed - as supplied by publisher]

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