Abstract
The orphan receptor TR3 is an important regulator of cell proliferation and apoptosis. However, whether TR3 is involved in regulating the stem-like properties of cancer cells remains unknown. The present study shows that TR3 expression is increased in gastric tumorsphere cells and is positively correlated with cancer stem cell (CSC) characteristics. Knocking down TR3 leads to the suppression of its stem-like properties in both gastric cancer cells and tumorsphere cells. This process involves the decreased expression of the stemness-related genes Oct-4 and Nanog and the invasion-related gene MMP-9. We further identify Nanog as a new target for the transcription factor TR3. Together, these data demonstrate for the first time that TR3 is essential for the maintenance of stem-like properties in human gastric cancer cells and implicate TR3 as a new therapeutic target for gastric cancer.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Base Sequence
-
Cell Line, Tumor
-
Gene Expression Regulation, Neoplastic
-
Gene Knockdown Techniques
-
Homeodomain Proteins / genetics
-
Humans
-
Matrix Metalloproteinase 9 / genetics
-
Mice
-
Mice, Inbred BALB C
-
Mice, Nude
-
Molecular Sequence Data
-
Nanog Homeobox Protein
-
Neoplastic Stem Cells / metabolism*
-
Neoplastic Stem Cells / pathology
-
Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
-
Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
-
Octamer Transcription Factor-3 / genetics
-
Promoter Regions, Genetic
-
Stomach Neoplasms / genetics
-
Stomach Neoplasms / metabolism*
-
Stomach Neoplasms / pathology*
-
Tumor Microenvironment / genetics
-
Xenograft Model Antitumor Assays
Substances
-
Homeodomain Proteins
-
NANOG protein, human
-
Nanog Homeobox Protein
-
Nuclear Receptor Subfamily 4, Group A, Member 1
-
Octamer Transcription Factor-3
-
POU5F1 protein, human
-
Matrix Metalloproteinase 9