Wnt-driven intestinal tumourigenesis is suppressed by Chk1 deficiency but enhanced by conditional haploinsufficiency

Greenow, K. R., Clarke, A. R. ORCID: https://orcid.org/0000-0002-4281-426X, Williams, G. T. ORCID: https://orcid.org/0000-0003-3768-9940 and Jones, R. ORCID: https://orcid.org/0000-0003-3576-9496 2014. Wnt-driven intestinal tumourigenesis is suppressed by Chk1 deficiency but enhanced by conditional haploinsufficiency. Oncogene 33 , pp. 4089-4096. 10.1038/onc.2013.371

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Abstract

Chk1 is essential in maintaining genomic stability due to its role in cell cycle regulation. Several recent studies have indicated that the abrogation of checkpoints in tumourigenesis through the inhibition of Chk1 may be of therapeutic value. To further investigate the role of Chk1 in the mouse small intestine and its potential role as a therapy for colorectal cancer, we simultaneously deleted Chk1 and Apc in the mouse small intestine. We found that homozygous loss of Chk1 is not compatible with Wnt-driven proliferation and resulted in the suppression of Wnt-driven tumourigenesis in the mouse small intestine. In contrast, heterozygous loss of Chk1 in a Wnt-driven background resulted in an increase in DNA damage and apoptosis and accelerated both tumour development and progression.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine European Cancer Stem Cell Research Institute (ECSCRI)
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	Chk1; Apc; genomic instability; small intestine; apoptosis
Publisher:	Springer Nature
ISSN:	0950-9232
Date of Acceptance:	7 June 2013
Last Modified:	25 Oct 2022 09:01
URI:	https://orca.cardiff.ac.uk/id/eprint/56879

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