Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients.
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ICR Authors
Authors
Chen, X
Legrand, AJ
Cunniffe, S
Hume, S
Poletto, M
Vaz, B
Ramadan, K
Yao, D
Dianov, GL
Legrand, AJ
Cunniffe, S
Hume, S
Poletto, M
Vaz, B
Ramadan, K
Yao, D
Dianov, GL
Document Type
Journal Article
Date
2018-10-01
Date Accepted
2018-06-08
Abstract
BACKGROUND: To deliver efficacious personalised cancer treatment, it is essential to characterise the cellular metabolism as well as the genetic stability of individual tumours. In this study, we describe a new axis between DNA repair and detoxification of aldehyde derivatives with important implications for patient prognosis and treatment. METHODS: Western blot and qPCR analyses were performed in relevant non-transformed and cancer cell lines from lung and liver tissue origin in combination with bioinformatics data mining of The Cancer Genome Atlas database from lung and hepatocellular cancer patients. RESULTS: Using both biochemical and bioinformatics approaches, we revealed an association between the levels of expression of the aldehyde detoxifying enzyme aldehyde dehydrogenase 2 (ALDH2) and the key DNA base excision repair protein XRCC1. Across cancer types, we found that if one of the corresponding genes exhibits a low expression level, the level of the other gene is increased. Surprisingly, we found that low ALDH2 expression levels associated with high XRCC1 expression levels are indicative for a poor overall survival, particularly in lung and liver cancer patients. In addition, we found that Mithramycin A, a XRCC1 expression inhibitor, efficiently kills cancer cells expressing low levels of ALDH2. CONCLUSIONS: Our data suggest that lung and liver cancers require efficient single-strand break repair for their growth in order to benefit from a low aldehyde detoxification metabolism. We also propose that the ratio of XRCC1 and ALDH2 levels may serve as a useful prognostic tool in these cancer types.
Citation
Cellular oncology (Dordrecht), 2018, 41 (5), pp. 527 - 539
Source Title
Publisher
SPRINGER
ISSN
2211-3428
eISSN
2211-3436
Collections
Research Team
Cell Death and Immunity