eprintid: 1400143
rev_number: 36
eprint_status: archive
userid: 608
dir: disk0/01/40/01/43
datestamp: 2013-07-22 18:46:32
lastmod: 2021-10-21 00:01:47
status_changed: 2014-08-01 11:41:57
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Mendes-Pereira, AM
creators_name: Lord, CJ
creators_name: Ashworth, A
title: NLK is a novel therapeutic target for PTEN deficient tumour cells
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
note: © 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
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.
date: 2012-10-29
official_url: http://dx.doi.org/10.1371/journal.pone.0047249
vfaculties: VFLS
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article, Research Support, Non-U.S. Gov't
verified: verified_manual
elements_source: PubMed
elements_id: 832477
doi: 10.1371/journal.pone.0047249
pii: PONE-D-12-14184
lyricists_name: Mendes Pereira, Ana Maria
lyricists_id: AMEND25
full_text_status: public
publication: PLoS One
volume: 7
number: 10
article_number: e47249
pagerange: -
event_location: United States
issn: 1932-6203
citation:        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 <https://doi.org/10.1371/journal.pone.0047249>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1400143/1/1373588.pdf