DUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator of intestinal cell proliferation and tumorigenesis
Tögel, Lars (La Trobe University School of Cancer Medicine)
Nightingale, Rebecca (La Trobe University School of Cancer Medicine)
Wu, Rui (Ludwig Institute for Cancer Research)
Chüeh, Anderly C. (Ludwig Institute for Cancer Research)
Al-Obaidi, Sheren (Ludwig Institute for Cancer Research)
Luk, Ian (La Trobe University School of Cancer Medicine)
Dávalos-Salas, Mercedes (La Trobe University School of Cancer Medicine)
Chionh, Fiona (La Trobe University School of Cancer Medicine)
Murone, Carmel (La Trobe University School of Cancer Medicine)
Buchanan, Daniel D. (The University of Melbourne)
Chatterton, Zac (The University of Melbourne)
Sieber, Oliver M. (The Walter and Eliza Hall Institute of Medical Research)
Arango, Diego (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Tebbutt, Niall C. (La Trobe University School of Cancer Medicine)
Williams, David (La Trobe University School of Cancer Medicine)
Dhillon, Amardeep S. (La Trobe University School of Cancer Medicine)
Mariadason, John M. (Ludwig Institute for Cancer Research)
Universitat Autònoma de Barcelona

Data:	2018
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Scientific reports, Vol. 8 (january 2018) , ISSN 2045-2322

Correccions a l'article: https://ddd.uab.cat/record/273344
DOI: 10.1038/s41598-018-20176-9
PMID: 29379130

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