Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17122
Title: DUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator of intestinal cell proliferation and tumorigenesis.
Authors: Tögel, Lars;Nightingale, Rebecca;Wu, Rui;Chüeh, Anderly C;Al-Obaidi, Sheren;Luk, Ian;Dávalos-Salas, Mercedes;Chionh, Fiona;Murone, Carmel;Buchanan, Daniel D;Chatterton, Zac;Sieber, Oliver M;Arango, Diego;Tebbutt, Niall C;Williams, David;Dhillon, Amardeep S;Mariadason, John M
Affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
La Trobe University School of Cancer Medicine, Melbourne, Australia
Ludwig Institute for Cancer Research, Melbourne, Australia
Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Melbourne, Australia..
Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia..
Group of Biomedical Research in Digestive Tract Tumours, CIBBIM-Nanomedicine, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain..
Issue Date: 29-Jan-2018
EDate: 2018
Citation: Scientific reports 2018; 8(1): 1767
Abstract: The ERK signalling pathway regulates key cell fate decisions in the intestinal epithelium and is frequently dysregulated in colorectal cancers (CRCs). Variations in the dynamics of ERK activation can induce different biological outcomes and are regulated by multiple mechanisms, including activation of negative feedback loops involving transcriptional induction of dual-specificity phosphatases (DUSPs). We have found that the nuclear ERK-selective phosphatase DUSP5 is downregulated in colorectal tumours and cell lines, as previously observed in gastric and prostate cancer. The DUSP5 promoter is methylated in a subset of CRC cell lines and primary tumours, particularly those with a CpG island methylator phenotype (CIMP). However, this epigenetic change alone could not account for reduced DUSP5 expression in CRC cells. Functionally, DUSP5 depletion failed to alter ERK signalling or proliferation in CRC cell lines, and its transgenic overexpression in the mouse intestine had minimal impact on normal intestinal homeostasis or tumour development. Our results suggest that DUSP5 plays a limited role in regulating ERK signalling associated with the growth of colorectal tumours, but that methylation the DUSP5 gene promoter can serve as an additional means of identifying CIMP-high colorectal cancers.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17122
DOI: 10.1038/s41598-018-20176-9
ORCID: http://orcid.org/0000-0003-2225-6675
http://orcid.org/0000-0003-2953-3284
PubMed URL: 29379130
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/29379130
Type: Journal Article
Appears in Collections:Journal articles

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