PMID- 23698634
OWN - NLM
STAT- MEDLINE
DCOM- 20131209
LR  - 20161125
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 34
IP  - 10
DP  - 2013 Oct
TI  - Histone demethylase KDM4C regulates sphere formation by mediating the cross talk 
      between Wnt and Notch pathways in colonic cancer cells.
PG  - 2380-8
LID - 10.1093/carcin/bgt174 [doi]
AB  - Alterations in genes coding for histone modifiers are found in human cancers, 
      suggesting that histone modification is involved in malignant features of 
      neoplastic cells. This study showed that a histone demethylase KDM4C is 
      significant for colonosphere formation by mediating the cross talk between 
      oncogenic pathways through a feed-forward mechanism. The expression of KDM4C gene 
      was increased in spheres from colorectal cancer (CRC) cells and the knockdown 
      (KD) of KDM4C eliminated colonosphere formation. We found that the KD of 
      beta-catenin, an important oncogenic factor in CRC, resulted in not only decreased 
      sphere formation but also impaired upregulation of KDM4C gene in spheres. 
      beta-Catenin bound to the KDM4C promoter, suggesting that KDM4C is involved in the 
      sphere-forming ability downstream of beta-catenin in CRC cells. Microarray analysis 
      identified the JAG1 gene that codes for a notch ligand Jagged1 responsible for 
      sphere formation as a target of KDM4C. KDM4C KD decreased the expression of JAG1 
      gene, and the downregulation of JAG1 gene recapitulated the impaired colonosphere 
      formation. JAG1 is also a target of beta-catenin, and chromatin immunoprecipitation 
      analysis showed the binding of beta-catenin and KDM4C onto the JAG1 promoter during 
      colonosphere formation. Importantly, KDM4C KD ruined the recruitment of beta-catenin 
      onto the JAG1 promoter independently of the H3-K9 methylation status and blunted 
      JAG1 expression during sphere formation. These data indicate that KDM4C maintains 
      the sphere-forming capacity in CRCs by mediating the beta-catenin-dependent 
      transcription of JAG1 in a feed-forward manner.
FAU - Yamamoto, Shinzo
AU  - Yamamoto S
AD  - Department of Gastroenterology, Graduate School of Medicine, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
FAU - Tateishi, Keisuke
AU  - Tateishi K
FAU - Kudo, Yotaro
AU  - Kudo Y
FAU - Yamamoto, Keisuke
AU  - Yamamoto K
FAU - Isagawa, Takayuki
AU  - Isagawa T
FAU - Nagae, Genta
AU  - Nagae G
FAU - Nakatsuka, Takuma
AU  - Nakatsuka T
FAU - Asaoka, Yoshinari
AU  - Asaoka Y
FAU - Ijichi, Hideaki
AU  - Ijichi H
FAU - Hirata, Yoshihiro
AU  - Hirata Y
FAU - Otsuka, Motoyuki
AU  - Otsuka M
FAU - Ikenoue, Tsuneo
AU  - Ikenoue T
FAU - Aburatani, Hiroyuki
AU  - Aburatani H
FAU - Omata, Masao
AU  - Omata M
FAU - Koike, Kazuhiko
AU  - Koike K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130522
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (JAG1 protein, human)
RN  - 0 (Jag1 protein, mouse)
RN  - 0 (Jagged-1 Protein)
RN  - 0 (KDM4C protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Notch)
RN  - 0 (Serrate-Jagged Proteins)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
SB  - IM
MH  - Animals
MH  - Calcium-Binding Proteins/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Colorectal Neoplasms/*genetics/*metabolism/pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - Heterografts
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Jagged-1 Protein
MH  - Jumonji Domain-Containing Histone Demethylases/*genetics/metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - Mice
MH  - Models, Biological
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - Receptors, Notch/*metabolism
MH  - Serrate-Jagged Proteins
MH  - *Signal Transduction
MH  - Spheroids, Cellular
MH  - Tumor Burden/genetics
MH  - Tumor Cells, Cultured
MH  - Wnt Proteins/*metabolism
MH  - beta Catenin/genetics/metabolism
EDAT- 2013/05/24 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/05/24 06:00
PHST- 2013/05/24 06:00 [entrez]
PHST- 2013/05/24 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - bgt174 [pii]
AID - 10.1093/carcin/bgt174 [doi]
PST - ppublish
SO  - Carcinogenesis. 2013 Oct;34(10):2380-8. doi: 10.1093/carcin/bgt174. Epub 2013 May 
      22.