Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility.
Although several therapeutic options are available for hepatocellular carcinoma (HCC), the outcome is still very poor. One reason is the complexity of signal transduction in the pathogenesis of HCC. The aim of this study was to identify new HCC-related genes and to investigate the functions of these genes in the pathogenesis and progression of HCC. Whole genomes of 15 surgically resected HCC specimens were examined for copy number alterations with comparative genomic hybridization. Gene expression was compared between HCC and normal liver tissues. The roles of the new genes in the progression of HCC were studied using cultured cell lines. Copy number gain in chromosome 8q was detected in 53% of HCC tissues examined. The gene that coded for collagen triple helix repeat containing 1 (CTHRC1), located at chromosome 8q22.3, was overexpressed in HCC compared with normal or liver cirrhosis tissues and identified as a new HCC-related gene. CTHRC1 deletion with short hairpin RNA significantly reduced proliferation, migration and invasion of HepG2 and Huh7 cells. In addition, mRNA of integrins β-2 and β-3 was downregulated, with deletion of CTHRC1 in these cells. Immunohistochemical staining on resected HCC tissues showing positive staining areas for CTHRC1 was significantly greater in poorly-differentiated HCC compared with well‑differentiated HCC. Moreover, some cases showed strong staining for CTHRC1 in invasive areas of HCC. CTHRC1 has the potential to be a new biomarker for the aggressive HCC, and to be a new therapeutic target in treating HCC.
First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Masahiko
M
Tameda
First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Kazushi
K
Sugimoto
First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Katsuya
K
Shiraki
First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Norihiko
N
Yamamoto
First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Ryuji
R
Okamoto
Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu 514-8507, Japan.
Masanobu
M
Usui
First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Masaaki
M
Ito
Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu 514-8507, Japan.
Yoshiyuki
Y
Takei
Department of Molecular and Laboratory Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Tsutomu
T
Nobori
Department of Molecular Biological Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Takahiro
T
Kojima
Research Division, MCBI, Tsukuba 305-0035, Japan.
Hideaki
H
Suzuki
Research Division, MCBI, Tsukuba 305-0035, Japan.
Masako
M
Uchida
Department of Molecular Biological Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Kazuhiko
K
Uchida
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D055028:Comparative Genomic Hybridization; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C502426:CTHRC1 protein, human; D016326:Extracellular Matrix Proteins