Open AccessInduction of LGR5 by H2O2 treatment is associated with cell proliferation via the JNK signaling pathway in colon cancer cells
Author(s) -
Sung Hee Kim,
Kyung Hee Kim,
Byong Chul Yoo,
JaLok Ku
Publication year - 2012
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2012.1596
Subject(s) - lgr5 , wnt signaling pathway , biology , stem cell , cancer research , microbiology and biotechnology , cell growth , cancer cell , signal transduction , cell cycle , oncogene , cancer stem cell , apoptosis , cancer , biochemistry , genetics
Recently, the leucine-rich repeat G protein-coupled receptor 5 (LGR5/GPR49)was identified as a potential marker of intestinal stem cells in human. The LGR5is known as a Wnt signaling target gene, and its expression pattern is relatedwith β-catenin mutation. H2O2 is a member of reactive oxygen species (ROS) andregulates metabolism, aging, apoptosis and the intensity of growth factor signaling.In addition, it acts as a negative or positive regulator of Wnt signaling. However,the effect of H2O2 on Wnt signaling and its target gene LGR5 is not clear. Inthis study, we investigated the effects of ROS on cancer stem cells, in colorectalcancer cells. Colorectal cancer cells were treated with exogenous H2O2, afterwhich cellular responses and the expression of LGR5 were examined. In SNU-C2Acells, proliferation increased following treatment with 50-300 µM of H2O2, whereascell viability significantly decreased after treatment with 600-900 µM of H2O2.Expression of heme oxygenase (HO)-1 and jun, which aid in the reduction of oxidativestress, were induced in the low dose H2O2-treated SNU-C2A cells. The LGR5 expressionlevel was significantly increased following 50-300 µM H2O2 treatment; in addition,β-catenin was increased in H2O2-treated colon cancer cells. However, the increasedβ-catenin was detected not in the nucleus but in the cytoplasm, which means thatβ-catenin was stabilized in the cytoplasm and not translocated into the nucleuswhere it could function as a transcription factor for the expression of LGR5.In addition, there was no direct interaction between LGR5 and β-catenin. In thisstudy, we found that LGR5 expression increased when cancer cells were treatedwith a low dose of H2O2. Our results indicate that the LGR5 increase resultedvia activation of the JNK signaling pathway. The induction of LGR5 expressioninfluenced cell proliferation in colorectal cancer cells.