PMID- 22025632
OWN - NLM
STAT- MEDLINE
DCOM- 20120325
LR  - 20111115
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 124
IP  - Pt 21
DP  - 2011 Nov 1
TI  - FAT10 mediates the effect of TNF-alpha in inducing chromosomal instability.
PG  - 3665-75
LID - 10.1242/jcs.087403 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays important roles in chronic 
      inflammation-associated tumorigenesis but the mechanisms involved remain poorly 
      understood. Previously, we reported that high levels of FAT10 led to chromosomal 
      instability that is mediated by an abbreviated mitotic phase. Here, we show that 
      TNF-alpha induces FAT10 gene expression through TNF receptor 1 (TNFR1) and activates 
      the NF-kappaB pathway in HCT116 and SW620 cells. TNF-alpha treatment also leads to an 
      abbreviated mitotic phase that can be reversed by inhibiting FAT10 expression. 
      This abbreviated mitotic phase is correlated with a TNF-alpha-induced reduction in 
      the kinetochore localization of MAD2 during prometaphase which, again, can be 
      reversed by inhibiting FAT10 gene expression. There is greater variability of 
      chromosome numbers in HCT116 and SW620 cells treated with TNF-alpha than in untreated 
      cells, which can be reversed by the introduction of short hairpin RNA (shRNA) 
      against FAT10. The more stable chromosome numbers in HCT116 cells expressing 
      FAT10 shRNA can revert to greater variability with the addition of a mutant FAT10 
      that is not recognized by the FAT10 shRNA. Upon TNF-alpha stimulation, higher cell 
      death is observed when FAT10 expression is inhibited by shRNA. These data 
      strongly suggest that FAT10 plays an important role in mediating the function of 
      TNF-alpha during tumorigenesis by inducing cell cycle deregulation and chromosomal 
      instability, and by inhibiting apoptosis.
FAU - Ren, Jianwei
AU  - Ren J
AD  - Department of Biochemistry, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore 119077, Singapore.
FAU - Wang, Yu
AU  - Wang Y
FAU - Gao, Yun
AU  - Gao Y
FAU - Mehta, Shalin B K
AU  - Mehta SB
FAU - Lee, Caroline G L
AU  - Lee CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111024
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (UBD protein, human)
RN  - 0 (Ubiquitins)
SB  - IM
MH  - Cell Cycle
MH  - Cell Line, Tumor
MH  - *Chromosomal Instability
MH  - Humans
MH  - Neoplasms/*genetics/metabolism/physiopathology
MH  - Receptors, Tumor Necrosis Factor, Type I/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
MH  - Ubiquitins/genetics/*metabolism
EDAT- 2011/10/26 06:00
MHDA- 2012/03/27 06:00
CRDT- 2011/10/26 06:00
PHST- 2011/10/26 06:00 [entrez]
PHST- 2011/10/26 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
AID - jcs.087403 [pii]
AID - 10.1242/jcs.087403 [doi]
PST - ppublish
SO  - J Cell Sci. 2011 Nov 1;124(Pt 21):3665-75. doi: 10.1242/jcs.087403. Epub 2011 Oct 
      24.