dc.contributor.author | Chen, X | |
dc.contributor.author | Legrand, AJ | |
dc.contributor.author | Cunniffe, S | |
dc.contributor.author | Hume, S | |
dc.contributor.author | Poletto, M | |
dc.contributor.author | Vaz, B | |
dc.contributor.author | Ramadan, K | |
dc.contributor.author | Yao, D | |
dc.contributor.author | Dianov, GL | |
dc.date.accessioned | 2018-08-09T13:26:18Z | |
dc.date.issued | 2018-10-01 | |
dc.identifier.citation | Cellular oncology (Dordrecht), 2018, 41 (5), pp. 527 - 539 | |
dc.identifier.issn | 2211-3428 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2312 | |
dc.identifier.eissn | 2211-3436 | |
dc.identifier.doi | 10.1007/s13402-018-0390-8 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 527 - 539 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGER | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Liver Neoplasms | |
dc.subject | Lung Neoplasms | |
dc.subject | DNA Damage | |
dc.subject | Plicamycin | |
dc.subject | RNA, Small Interfering | |
dc.subject | Cell Survival | |
dc.subject | Aldehyde Dehydrogenase, Mitochondrial | |
dc.subject | X-ray Repair Cross Complementing Protein 1 | |
dc.title | Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-06-08 | |
rioxxterms.versionofrecord | 10.1007/s13402-018-0390-8 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cellular oncology (Dordrecht) | |
pubs.issue | 5 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity | |
pubs.publication-status | Published | |
pubs.volume | 41 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Cell Death and Immunity | |
dc.contributor.icrauthor | Legrand, Arnaud | |