Tanabe S, Kawabata T, Aoyagi K, Yokozaki H, Sasaki H. Gene expression and pathway analysis of CTNNB1 in cancer and stem cells. World J Stem Cells 2016; 8(11): 384-395 [PMID: 27928465 DOI: 10.4252/wjsc.v8.i11.384]
Corresponding Author of This Article
Shihori Tanabe, PhD, Division of Risk Assessment, National Institute of Health Sciences, 1-18-1, Kami-yoga, Setagaya-ku, Tokyo 158-8501, Japan. stanabe@nihs.go.jp
Research Domain of This Article
Cell Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Shihori Tanabe, Division of Risk Assessment, National Institute of Health Sciences, Tokyo 158-8501, Japan
Takeshi Kawabata, Laboratory of Protein Informatics, Institute for Protein Research, Osaka University, Suita 565-0871, Japan
Kazuhiko Aoyagi, Hiroki Sasaki, Department of Translational Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Hiroshi Yokozaki, Department of Pathology, Kobe University of Graduate School of Medicine, Kobe 650-0017, Japan
Author contributions: Tanabe S performed the research and wrote the paper; Kawabata T analyzed the 3D structures of proteins; Aoyagi K, Yokozaki H and Sasaki H contributed critical revision of the manuscript for important intellectual content.
Institutional review board statement: Diffuse-type gastric cancer (GC) tissues were originally provided by the National Cancer Center Hospital after obtaining written informed consent from each patient and approval by National Cancer Center Institutional Review Board (ID: No.17-030). The existing data already available to the public were analyzed in the article.
Informed consent statement: Written informed consent from each patient were obtained.
Conflict-of-interest statement: To the best of the authors’ knowledge, no conflict of interest exists.
Data sharing statement: The microarray data for mesenchymal stem cells and diffuse-type gastric cancer are available to the public in NCBI’s Gene Expression Omnibus (GEO) database and are accessible via GEO Series accession number GSE7888 and GSE42252, respectively.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shihori Tanabe, PhD, Division of Risk Assessment, National Institute of Health Sciences, 1-18-1, Kami-yoga, Setagaya-ku, Tokyo 158-8501, Japan. stanabe@nihs.go.jp
Telephone: +81-3-37001141 Fax: +81-3-37001145
Received: May 30, 2016 Peer-review started: June 3, 2016 First decision: July 5, 2016 Revised: July 22, 2016 Accepted: September 21, 2016 Article in press: September 22, 2016 Published online: November 26, 2016 Processing time: 174 Days and 21.6 Hours
Abstract
AIM
To investigate β-catenin (CTNNB1) signaling in cancer and stem cells, the gene expression and pathway were analyzed using bioinformatics.
METHODS
The expression of the catenin β 1 (CTNNB1) gene, which codes for β-catenin, was analyzed in mesenchymal stem cells (MSCs) and gastric cancer (GC) cells. Beta-catenin signaling and the mutation of related proteins were also analyzed using the cBioPortal for Cancer Genomics and HOMology modeling of Complex Structure (HOMCOS) databases.
RESULTS
The expression of the CTNNB1 gene was up-regulated in GC cells compared to MSCs. The expression of EPH receptor A8 (EPHA8), synovial sarcoma translocation chromosome 18 (SS18), interactor of little elongation complex ELL subunit 1 (ICE1), patched 1 (PTCH1), mutS homolog 3 (MSH3) and caspase recruitment domain family member 11 (CARD11) were also shown to be altered in GC cells in the cBioPortal for Cancer Genomics analysis. 3D complex structures were reported for E-cadherin 1 (CDH1), lymphoid enhancer binding factor 1 (LEF1), transcription factor 7 like 2 (TCF7L2) and adenomatous polyposis coli protein (APC) with β-catenin.
CONCLUSION
The results indicate that the epithelial-mesenchymal transition (EMT)-related gene CTNNB1 plays an important role in the regulation of stem cell pluripotency and cancer signaling.
Core tip: β-catenin signaling consists of several pathway cascades, such as those that are involved in pluripotent stem cell generation and cancer. Several genes, including EPHA8, SS18, ICE1, PTCH1, MSH3 and CARD11, are mutated along with CTNNB1. The expression of the CTNNB1, CDH1, MYC, LEF1 and TCF7L2 genes, which are related to the CTNNB1 network, is up-regulated in diffuse-type GC cells compared to MSCs. 3D complex structures for β-catenin (CTNB1_HUMAN) with LEF_MOUSE and TF7L2_HUMAN were found using the HOMCOS database. The EMT-related gene CTNNB1 plays an important role in pluripotent stem cell signaling and cancer signaling.
