Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells

Glycogen-specific kinase (GSK3β) is an integral regulator of the Wnt signalling pathway as well as many other diverse signalling pathways and processes. Dys-regulation of GSK3β is implicated in many different pathologies, including neurodegenerative disorders as well as many different tumour types....

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Autores principales:	Emily Bowler-Barnett, Francisco D. Martinez-Garcia, Matthew Sherwood, Ahood Aleidan, Steve John, Sara Weston, Yihua Wang, Nullin Divecha, Paul Skipp, Rob M. Ewing
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e68adf85ed884abebca793ef6ffd3672
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spelling	oai:doaj.org-article:e68adf85ed884abebca793ef6ffd36722021-11-11T07:14:35ZProteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells1932-6203https://doaj.org/article/e68adf85ed884abebca793ef6ffd36722021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570494/?tool=EBIhttps://doaj.org/toc/1932-6203Glycogen-specific kinase (GSK3β) is an integral regulator of the Wnt signalling pathway as well as many other diverse signalling pathways and processes. Dys-regulation of GSK3β is implicated in many different pathologies, including neurodegenerative disorders as well as many different tumour types. In the context of tumour development, GSK3β has been shown to play both oncogenic and tumour suppressor roles, depending upon tissue, signalling environment or disease progression. Although multiple substrates of the GSK3β kinase have been identified, the wider protein networks within which GSK3β participates are not well known, and the consequences of these interactions not well understood. In this study, LC-MS/MS expression analysis was performed using knockout GSK3β colorectal cancer cells and isogenic controls in colorectal cancer cell lines carrying dominant stabilizing mutations of β-catenin. Consistent with the role of GSK3β, we found that β-catenin levels and canonical Wnt activity are unaffected by knockout of GSK3β and therefore used this knockout cell model to identify other processes in which GSK3β is implicated. Quantitative proteomic analysis revealed perturbation of proteins involved in cell-cell adhesion, and we characterized the phenotype and altered proteomic profiles associated with this. We also characterized the perturbation of metabolic pathways resulting from GSK3β knockout and identified defects in glycogen metabolism. In summary, using a precision colorectal cancer cell-line knockout model with constitutively activated β-catenin we identified several of the diverse pathways and processes associated with GSK3β function.Emily Bowler-BarnettFrancisco D. Martinez-GarciaMatthew SherwoodAhood AleidanSteve JohnSara WestonYihua WangNullin DivechaPaul SkippRob M. EwingPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emily Bowler-Barnett Francisco D. Martinez-Garcia Matthew Sherwood Ahood Aleidan Steve John Sara Weston Yihua Wang Nullin Divecha Paul Skipp Rob M. Ewing Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells
description	Glycogen-specific kinase (GSK3β) is an integral regulator of the Wnt signalling pathway as well as many other diverse signalling pathways and processes. Dys-regulation of GSK3β is implicated in many different pathologies, including neurodegenerative disorders as well as many different tumour types. In the context of tumour development, GSK3β has been shown to play both oncogenic and tumour suppressor roles, depending upon tissue, signalling environment or disease progression. Although multiple substrates of the GSK3β kinase have been identified, the wider protein networks within which GSK3β participates are not well known, and the consequences of these interactions not well understood. In this study, LC-MS/MS expression analysis was performed using knockout GSK3β colorectal cancer cells and isogenic controls in colorectal cancer cell lines carrying dominant stabilizing mutations of β-catenin. Consistent with the role of GSK3β, we found that β-catenin levels and canonical Wnt activity are unaffected by knockout of GSK3β and therefore used this knockout cell model to identify other processes in which GSK3β is implicated. Quantitative proteomic analysis revealed perturbation of proteins involved in cell-cell adhesion, and we characterized the phenotype and altered proteomic profiles associated with this. We also characterized the perturbation of metabolic pathways resulting from GSK3β knockout and identified defects in glycogen metabolism. In summary, using a precision colorectal cancer cell-line knockout model with constitutively activated β-catenin we identified several of the diverse pathways and processes associated with GSK3β function.
format	article
author	Emily Bowler-Barnett Francisco D. Martinez-Garcia Matthew Sherwood Ahood Aleidan Steve John Sara Weston Yihua Wang Nullin Divecha Paul Skipp Rob M. Ewing
author_facet	Emily Bowler-Barnett Francisco D. Martinez-Garcia Matthew Sherwood Ahood Aleidan Steve John Sara Weston Yihua Wang Nullin Divecha Paul Skipp Rob M. Ewing
author_sort	Emily Bowler-Barnett
title	Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells
title_short	Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells
title_full	Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells
title_fullStr	Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells
title_full_unstemmed	Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells
title_sort	proteomic characterization of gsk3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e68adf85ed884abebca793ef6ffd3672
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_version_	1718439451691057152

Proteomic characterization of GSK3β knockout shows altered cell adhesion and metabolic pathway utilisation in colorectal cancer cells

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