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PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling

BACKGROUND: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) regulation of the Rho-like GTPase Cdc42 has a central role in epithelial polarised growth, but effects of this molecular network on apoptosis remain unclear. METHODS: To investigate the role of Cdc42 in PTEN-dependent cell...

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Autores principales: Deevi, R, Fatehullah, A, Jagan, I, Nagaraju, M, Bingham, V, Campbell, F C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241554/
https://www.ncbi.nlm.nih.gov/pubmed/21952626
http://dx.doi.org/10.1038/bjc.2011.384
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author Deevi, R
Fatehullah, A
Jagan, I
Nagaraju, M
Bingham, V
Campbell, F C
author_facet Deevi, R
Fatehullah, A
Jagan, I
Nagaraju, M
Bingham, V
Campbell, F C
author_sort Deevi, R
collection PubMed
description BACKGROUND: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) regulation of the Rho-like GTPase Cdc42 has a central role in epithelial polarised growth, but effects of this molecular network on apoptosis remain unclear. METHODS: To investigate the role of Cdc42 in PTEN-dependent cell death, we used flow cytometry, in vitro pull-down assays, poly(ADP ribose) polymerase (PARP) cleavage and other immunoblots in isogenic PTEN-expressing and -deficient colorectal cells (HCT116PTEN(+/+), HCT116PTEN(−/−), Caco2 and Caco2 ShPTEN cells) after transfection or treatment strategies. RESULTS: The PTEN knockout or suppression by short hairpin RNA or small interfering RNA (siRNA) inhibited Cdc42 activity, PARP cleavage and/or apoptosis in flow cytometry assays. Transfection of cells with wild-type or constitutively active Cdc42 enhanced PARP cleavage, whereas siRNA silencing of Cdc42 inhibited PARP cleavage and/or apoptosis. Pharmacological upregulation of PTEN by sodium butyrate (NaBt) treatment enhanced Cdc42 activity, PARP cleavage and apoptosis, whereas Cdc42 siRNA suppressed NaBt-induced PARP cleavage. Cdc42-dependent signals can suppress glycogen synthase kinase-β (GSK3β) activity. Pharmacological inhibition of GSK3β by lithium chloride treatment mimicked effects of Cdc42 in promotion of PARP cleavage and/or apoptosis. CONCLUSION: Phosphatase and tensin homologue deleted on chromosome 10 may influence apoptosis in colorectal epithelium through Cdc42 signalling, thus providing a regulatory framework for both polarised growth and programmed cell death.
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spelling pubmed-32415542012-10-25 PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling Deevi, R Fatehullah, A Jagan, I Nagaraju, M Bingham, V Campbell, F C Br J Cancer Translational Therapeutics BACKGROUND: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) regulation of the Rho-like GTPase Cdc42 has a central role in epithelial polarised growth, but effects of this molecular network on apoptosis remain unclear. METHODS: To investigate the role of Cdc42 in PTEN-dependent cell death, we used flow cytometry, in vitro pull-down assays, poly(ADP ribose) polymerase (PARP) cleavage and other immunoblots in isogenic PTEN-expressing and -deficient colorectal cells (HCT116PTEN(+/+), HCT116PTEN(−/−), Caco2 and Caco2 ShPTEN cells) after transfection or treatment strategies. RESULTS: The PTEN knockout or suppression by short hairpin RNA or small interfering RNA (siRNA) inhibited Cdc42 activity, PARP cleavage and/or apoptosis in flow cytometry assays. Transfection of cells with wild-type or constitutively active Cdc42 enhanced PARP cleavage, whereas siRNA silencing of Cdc42 inhibited PARP cleavage and/or apoptosis. Pharmacological upregulation of PTEN by sodium butyrate (NaBt) treatment enhanced Cdc42 activity, PARP cleavage and apoptosis, whereas Cdc42 siRNA suppressed NaBt-induced PARP cleavage. Cdc42-dependent signals can suppress glycogen synthase kinase-β (GSK3β) activity. Pharmacological inhibition of GSK3β by lithium chloride treatment mimicked effects of Cdc42 in promotion of PARP cleavage and/or apoptosis. CONCLUSION: Phosphatase and tensin homologue deleted on chromosome 10 may influence apoptosis in colorectal epithelium through Cdc42 signalling, thus providing a regulatory framework for both polarised growth and programmed cell death. Nature Publishing Group 2011-10-25 2011-09-27 /pmc/articles/PMC3241554/ /pubmed/21952626 http://dx.doi.org/10.1038/bjc.2011.384 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Translational Therapeutics
Deevi, R
Fatehullah, A
Jagan, I
Nagaraju, M
Bingham, V
Campbell, F C
PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling
title PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling
title_full PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling
title_fullStr PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling
title_full_unstemmed PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling
title_short PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling
title_sort pten regulates colorectal epithelial apoptosis through cdc42 signalling
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241554/
https://www.ncbi.nlm.nih.gov/pubmed/21952626
http://dx.doi.org/10.1038/bjc.2011.384
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