The osteopontin-CD44 axis in hepatic cancer stem cells regulates IFN signaling and HCV replication

Autor: Taro Yamashita, Takayoshi Shirasaki, Tetsuro Suzuki, Masao Honda, Ryougo Shimizu, Katsuji Yoshioka, Tokiharu Sato, Saki Nakasyo, Tetsuro Shimakami, Kouki Nio, Natsumi Shirasaki, Kazuhisa Murai, Shuichi Kaneko, Yoshio Sakai, Hikari Okada
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
lcsh:Medicine
Hepacivirus
Virus Replication
chemistry.chemical_compound
Interferon
Cell Movement
Osteopontin
Phosphorylation
lcsh:Science
education.field_of_study
Multidisciplinary
biology
Chemistry
Liver Neoplasms
Epithelial cell adhesion molecule
Epithelial Cell Adhesion Molecule
Hepatitis C
Gene Expression Regulation
Neoplastic
Hyaluronan Receptors
STAT1 Transcription Factor
Liver
Host-Pathogen Interactions
Neoplastic Stem Cells
Stem cell
medicine.drug
Signal Transduction
Carcinoma
Hepatocellular
Population
Article
03 medical and health sciences
stomatognathic system
Cancer stem cell
Cell Line
Tumor
medicine
Humans
education
Protein Kinase Inhibitors
Cell Proliferation
Glycogen Synthase Kinase 3 beta
CD44
lcsh:R
Interferon-alpha
030104 developmental biology
Viral replication
biology.protein
Cancer research
Hepatocytes
lcsh:Q
Zdroj: Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
Scientific Reports
ISSN: 2045-2322
Popis: Osteopontin (OPN) is involved in cell proliferation, migration, inflammation, and tumor progression in various tissues. OPN induces stemness by interacting with CD44, but the functional relevance of OPN-mediated interferon (IFN) signaling and hepatitis C virus (HCV) replication in stem cell populations remains unclear. In this study, we investigated the effect of OPN on HCV replication and IFN signaling in cancer stem cells (CSCs) positive for epithelial cell adhesion molecule (EpCAM) and CD44. We show that the EpCAM+/CD44+ CSCs show marked HCV replication when compared to EpCAM−/CD44− cells. In addition, OPN significantly enhances this HCV replication in EpCAM+/CD44+ CSCs and markedly suppresses IFN-stimulated gene expression. The GSK-3β inhibitor BIO increases the EpCAM+/CD44+ CSC population and OPN expression and impairs IFN signaling via STAT1 degradation. Taken together, our data suggest that OPN enhances HCV replication in the EpCAM+/CD44+ CSCs, while it also negatively regulates the IFN signaling pathway via inhibition of STAT1 phosphorylation and degradation. Therefore, OPN may represent a novel therapeutic target for treating HCV-related hepatocellular carcinoma.
Databáze: OpenAIRE
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