NLK is a novel therapeutic target for PTEN deficient tumour cells.

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 o...

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Autores principales:	Ana M Mendes-Pereira, Christopher J Lord, Alan Ashworth
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b1c5800cf294b4893d83204f84bf90b
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spelling	oai:doaj.org-article:6b1c5800cf294b4893d83204f84bf90b2021-11-18T08:10:48ZNLK is a novel therapeutic target for PTEN deficient tumour cells.1932-620310.1371/journal.pone.0047249https://doaj.org/article/6b1c5800cf294b4893d83204f84bf90b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23144700/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203PTEN (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.Ana M Mendes-PereiraChristopher J LordAlan AshworthPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e47249 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana M Mendes-Pereira Christopher J Lord Alan Ashworth NLK is a novel therapeutic target for PTEN deficient tumour cells.
description	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.
format	article
author	Ana M Mendes-Pereira Christopher J Lord Alan Ashworth
author_facet	Ana M Mendes-Pereira Christopher J Lord Alan Ashworth
author_sort	Ana M Mendes-Pereira
title	NLK is a novel therapeutic target for PTEN deficient tumour cells.
title_short	NLK is a novel therapeutic target for PTEN deficient tumour cells.
title_full	NLK is a novel therapeutic target for PTEN deficient tumour cells.
title_fullStr	NLK is a novel therapeutic target for PTEN deficient tumour cells.
title_full_unstemmed	NLK is a novel therapeutic target for PTEN deficient tumour cells.
title_sort	nlk is a novel therapeutic target for pten deficient tumour cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6b1c5800cf294b4893d83204f84bf90b
work_keys_str_mv	AT anammendespereira nlkisanoveltherapeutictargetforptendeficienttumourcells AT christopherjlord nlkisanoveltherapeutictargetforptendeficienttumourcells AT alanashworth nlkisanoveltherapeutictargetforptendeficienttumourcells
_version_	1718422113074806784

NLK is a novel therapeutic target for PTEN deficient tumour cells.

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