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dc.contributor.authorTogel, L
dc.contributor.authorNightingale, R
dc.contributor.authorWu, R
dc.contributor.authorChueh, AC
dc.contributor.authorAl-Obaidi, S
dc.contributor.authorLuk, I
dc.contributor.authorDavalos-Salas, M
dc.contributor.authorChionh, F
dc.contributor.authorMurone, C
dc.contributor.authorBuchanan, DD
dc.contributor.authorChatterton, Z
dc.contributor.authorSieber, OM
dc.contributor.authorArango, D
dc.contributor.authorTebbutt, NC
dc.contributor.authorWilliams, D
dc.contributor.authorDhillon, AS
dc.contributor.authorMariadason, JM
dc.date.accessioned2020-12-09T22:57:45Z
dc.date.available2020-12-09T22:57:45Z
dc.date.issued2018-01-29
dc.identifierpii: 10.1038/s41598-018-20176-9
dc.identifier.citationTogel, L., Nightingale, R., Wu, R., Chueh, A. C., Al-Obaidi, S., Luk, I., Davalos-Salas, M., Chionh, F., Murone, C., Buchanan, D. D., Chatterton, Z., Sieber, O. M., Arango, D., Tebbutt, N. C., Williams, D., Dhillon, A. S. & Mariadason, J. M. (2018). DUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator of intestinal cell proliferation and tumorigenesis. SCIENTIFIC REPORTS, 8 (1), https://doi.org/10.1038/s41598-018-20176-9.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/253103
dc.description.abstractThe 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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleDUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator of intestinal cell proliferation and tumorigenesis
dc.typeJournal Article
dc.identifier.doi10.1038/s41598-018-20176-9
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.departmentMedical Education
melbourne.affiliation.departmentPathology
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.departmentSurgery (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleScientific Reports
melbourne.source.volume8
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1300445
melbourne.contributor.authorChueh, Anderly
melbourne.contributor.authorBuchanan, Daniel
melbourne.contributor.authorMariadason, John
melbourne.contributor.authorLuk, Ian
melbourne.contributor.authorChionh, Fiona
melbourne.contributor.authorTebbutt, Niall
melbourne.contributor.authorSieber, Oliver
melbourne.contributor.authorTOGEL, LARS
melbourne.contributor.authorMurone, Carmelina
melbourne.contributor.authorWU, RUI
melbourne.contributor.authorCHATTERTON, ZAC
melbourne.contributor.authorWilliams, David
melbourne.contributor.authorChionh, Fiona
dc.identifier.eissn2045-2322
melbourne.accessrightsOpen Access


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