PMID- 25772234
OWN - NLM
STAT- MEDLINE
DCOM- 20160525
LR  - 20181113
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 35
IP  - 2
DP  - 2016 Jan 14
TI  - DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis.
PG  - 206-17
LID - 10.1038/onc.2015.74 [doi]
AB  - Dual specificity phosphatase 10 (DUSP10), also known as MAP kinase phosphatase 5 
      (MKP5), negatively regulates the activation of MAP kinases. Genetic polymorphisms 
      and aberrant expression of this gene are associated with colorectal cancer (CRC) 
      in humans. However, the role of DUSP10 in intestinal epithelial tumorigenesis is 
      not clear. Here, we showed that DUSP10 knockout (KO) mice had increased 
      intestinal epithelial cell (IEC) proliferation and migration and developed less 
      severe colitis than wild-type (WT) mice in response to dextran sodium sulphate 
      (DSS) treatment, which is associated with increased ERK1/2 activation and 
      Kruppel-like factor 5 (KLF5) expression in IEC. In line with increased IEC 
      proliferation, DUSP10 KO mice developed more colon tumours with increased 
      severity compared with WT mice in response to administration of DSS and 
      azoxymethane (AOM). Furthermore, survival analysis of CRC patients demonstrated 
      that high DUSP10 expression in tumours was associated with significant 
      improvement in survival probability. Overexpression of DUSP10 in Caco-2 and RCM-1 
      cells inhibited cell proliferation. Our study showed that DUSP10 negatively 
      regulates IEC growth and acts as a suppressor for CRC. Therefore, it could be 
      targeted for the development of therapies for colitis and CRC.
FAU - Png, C W
AU  - Png CW
AD  - Department of Microbiology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, Singapore.
AD  - Immunology Programme, Life Science Institute, National University of Singapore, 
      Singapore, Singapore.
FAU - Weerasooriya, M
AU  - Weerasooriya M
AD  - Department of Microbiology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, Singapore.
AD  - Immunology Programme, Life Science Institute, National University of Singapore, 
      Singapore, Singapore.
FAU - Guo, J
AU  - Guo J
AD  - Cancer Science Institute of Singapore, National University of Singapore, 
      Singapore, Singapore.
FAU - James, S J
AU  - James SJ
AD  - Department of Microbiology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, Singapore.
AD  - Immunology Programme, Life Science Institute, National University of Singapore, 
      Singapore, Singapore.
FAU - Poh, H M
AU  - Poh HM
AD  - Department of Microbiology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, Singapore.
AD  - Immunology Programme, Life Science Institute, National University of Singapore, 
      Singapore, Singapore.
FAU - Osato, M
AU  - Osato M
AD  - Cancer Science Institute of Singapore, National University of Singapore, 
      Singapore, Singapore.
FAU - Flavell, R A
AU  - Flavell RA
AD  - Department of Immunology, Howard Hughes Medical Institute, Yale University, New 
      Haven, CT, USA.
FAU - Dong, C
AU  - Dong C
AD  - Department of Basic Medical Sciences, Tsinghua University School of Medicine, 
      Beijing, China.
FAU - Yang, H
AU  - Yang H
AD  - Cancer Science Institute of Singapore, National University of Singapore, 
      Singapore, Singapore.
FAU - Zhang, Y
AU  - Zhang Y
AD  - Department of Microbiology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore, Singapore.
AD  - Immunology Programme, Life Science Institute, National University of Singapore, 
      Singapore, Singapore.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150316
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Klf5 protein, mouse)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.1.3.16 (DUSP10 protein, human)
RN  - EC 3.1.3.16 (Dusp10 protein, mouse)
RN  - EC 3.1.3.16 (Mitogen-Activated Protein Kinase Phosphatases)
RN  - EC 3.1.3.48 (Dual-Specificity Phosphatases)
SB  - IM
MH  - Animals
MH  - Caco-2 Cells
MH  - Cell Proliferation/genetics
MH  - Colitis/chemically induced/genetics/pathology
MH  - Colorectal Neoplasms/genetics/mortality/*pathology
MH  - Dextran Sulfate/toxicity
MH  - Dual-Specificity Phosphatases/*genetics/*metabolism
MH  - Epithelial Cells/metabolism/pathology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - Intestines/cytology
MH  - Kruppel-Like Transcription Factors/genetics/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinase Phosphatases/*genetics/metabolism
MH  - Survival Rate
MH  - Xenograft Model Antitumor Assays
EDAT- 2015/03/17 06:00
MHDA- 2016/05/26 06:00
CRDT- 2015/03/17 06:00
PHST- 2014/08/30 00:00 [received]
PHST- 2015/01/04 00:00 [revised]
PHST- 2015/02/05 00:00 [accepted]
PHST- 2015/03/17 06:00 [entrez]
PHST- 2015/03/17 06:00 [pubmed]
PHST- 2016/05/26 06:00 [medline]
AID - onc201574 [pii]
AID - 10.1038/onc.2015.74 [doi]
PST - ppublish
SO  - Oncogene. 2016 Jan 14;35(2):206-17. doi: 10.1038/onc.2015.74. Epub 2015 Mar 16.