Mendes-Pereira, AM;
Lord, CJ;
Ashworth, A;
(2012)
NLK is a novel therapeutic target for PTEN deficient tumour cells.
PLoS One
, 7
(10)
, Article e47249. 10.1371/journal.pone.0047249.
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Abstract
PTEN (Phosphatase and tensin homolog) is a tumour suppressor gene commonly defective in human cancer, and is thus a potentially important therapeutic target. Targeting tumour suppressor loss-of-function is possible by exploiting the genetic concept of synthetic lethality (SL). By combining the use of isogenic models of PTEN deficiency with high-throughput RNA interference (RNAi) screening, we have identified Nemo-Like Kinase (NLK) inhibition as being synthetically lethal with PTEN deficiency. This SL is likely mediated by the transcription factor FOXO1 (Forkhead box O1), an NLK substrate, as the selectivity of NLK gene silencing for PTEN deficient cells can be reversed by FOXO1 knockdown. In addition, we provide evidence that PTEN defective cells targeted by NLK gene depletion undergo senescence, suggesting that NLK function is critical for the continued proliferation of PTEN deficient cells. Taken together, these data provide new insight into the potential of targeting of NLK to treat a range of tumourigenic conditions characterised by PTEN deficiency.
| Type: | Article |
|---|---|
| Title: | NLK is a novel therapeutic target for PTEN deficient tumour cells |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0047249 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0047249 |
| Language: | English |
| Additional information: | © 2012 Mendes-Pereira et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3483146 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1400143 |
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