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The inflammatory mediator leukotriene D4 induces subcellular β-catenin translocation and migration of colon cancer cells.

Salim, Tavga LU ; Sand-Dejmek, Janna LU and Sjölander, Anita LU (2014) In Experimental Cell Research 321(2). p.255-266
Abstract
The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D4 (LTD4) exerts its effects through the CysLT1 receptor. We previously reported an upregulation of CysLT1R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD4 on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD4 stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent... (More)
The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D4 (LTD4) exerts its effects through the CysLT1 receptor. We previously reported an upregulation of CysLT1R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD4 on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD4 stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD4 significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD4 can be blocked by the inhibition of CysLT1R. Furthermore, LTD4 induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT1 and the Wnt/β-catenin pathway. In conclusion, LTD4, which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Cell Research
volume
321
issue
2
pages
255 - 266
publisher
Academic Press
external identifiers
  • pmid:24211746
  • wos:000331419300016
  • scopus:84895062242
ISSN
1090-2422
DOI
10.1016/j.yexcr.2013.10.021
language
English
LU publication?
yes
id
87123e9f-7ac4-4dd6-8e02-605ad72cf0f2 (old id 4179601)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24211746?dopt=Abstract
date added to LUP
2013-12-04 14:28:00
date last changed
2017-09-10 03:00:39
@article{87123e9f-7ac4-4dd6-8e02-605ad72cf0f2,
  abstract     = {The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D4 (LTD4) exerts its effects through the CysLT1 receptor. We previously reported an upregulation of CysLT1R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD4 on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD4 stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD4 significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD4 can be blocked by the inhibition of CysLT1R. Furthermore, LTD4 induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT1 and the Wnt/β-catenin pathway. In conclusion, LTD4, which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells.},
  author       = {Salim, Tavga and Sand-Dejmek, Janna and Sjölander, Anita},
  issn         = {1090-2422},
  language     = {eng},
  number       = {2},
  pages        = {255--266},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {The inflammatory mediator leukotriene D4 induces subcellular β-catenin translocation and migration of colon cancer cells.},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2013.10.021},
  volume       = {321},
  year         = {2014},
}