Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep22371
Title: Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination
Authors: Kurashige, J
Hasegawa, T
Niida, A
Sugimachi, K
Deng, N 
Mima, K
Uchi, R
Sawada, G
Takahashi, Y
Eguchi, H
Inomata, M
Kitano, S
Fukagawa, T
Sasako, M
Sasaki, H
Sasaki, S
Mori, M
Yanagihara, K
Baba, H
Miyano, S
Tan, P 
Mimori, K
Keywords: dasatinib
DDR2 protein, human
discoidin domain receptor 2
tumor protein
animal
Bagg albino mouse
cancer transplantation
enzymology
female
gene expression profiling
genetics
human
male
metabolism
metastasis
mouse
nude mouse
pathology
peritoneum tumor
secondary
signal transduction
stomach tumor
tumor cell line
xenograft
Animals
Cell Line, Tumor
Dasatinib
Discoidin Domain Receptor 2
Female
Gene Expression Profiling
Heterografts
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Metastasis
Neoplasm Proteins
Neoplasm Transplantation
Peritoneal Neoplasms
Signal Transduction
Stomach Neoplasms
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Kurashige, J, Hasegawa, T, Niida, A, Sugimachi, K, Deng, N, Mima, K, Uchi, R, Sawada, G, Takahashi, Y, Eguchi, H, Inomata, M, Kitano, S, Fukagawa, T, Sasako, M, Sasaki, H, Sasaki, S, Mori, M, Yanagihara, K, Baba, H, Miyano, S, Tan, P, Mimori, K (2016). Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination. Scientific Reports 6 : 22371. ScholarBank@NUS Repository. https://doi.org/10.1038/srep22371
Abstract: Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/174987
ISSN: 20452322
DOI: 10.1038/srep22371
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_srep22371.pdf6.69 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

26
checked on Dec 4, 2020

Page view(s)

79
checked on Dec 4, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.