RRC ID 44878
Author Okamoto T, Iwata S, Yamazaki H, Hatano R, Komiya E, Dang NH, Ohnuma K, Morimoto C.
Title CD9 negatively regulates CD26 expression and inhibits CD26-mediated enhancement of invasive potential of malignant mesothelioma cells.
Journal PLoS One
Abstract CD26/dipeptidyl peptidase IV is a cell surface glycoprotein which consists of multiple functional domains beside its ectopeptidase site. A growing body of evidence indicates that elevated expression of CD26 correlates with disease aggressiveness and invasive potential of selected malignancies. To further explore the molecular mechanisms involved in this clinical behavior, our current work focused on the interaction between CD26 and CD9, which were recently identified as novel markers for cancer stem cells in malignant mesothelioma. We found that CD26 and CD9 co-modulated and co-precipitated with each other in the malignant mesothelioma cell lines ACC-MESO1 and MSTO-211H. SiRNA study revealed that depletion of CD26 led to increased CD9 expression, while depletion of CD9 resulted in increased CD26 expression. Consistent with these findings was the fact that gene transfer of CD26 into CD26-negative MSTO-211H cells reduced CD9 expression. Cell invasion assay showed that overexpression of CD26 or gene depletion of CD9 led to enhanced invasiveness, while CD26 gene depletion resulted in reduced invasive potential. Furthermore, our work suggested that this enhanced invasiveness may be partly mediated by α5β1 integrin, since co-precipitation studies demonstrated an association between CD26 and α5β1 integrin. Finally, gene depletion of CD9 resulted in elevated protein levels and tyrosine phosphorylation of FAK and Cas-L, which are downstream of β1 integrin, while depletion of CD26 led to a reduction in the levels of these molecules. Collectively, our findings suggest that CD26 potentiates tumor cell invasion through its interaction with α5β1 integrin, and CD9 negatively regulates tumor cell invasion by reducing the level of CD26-α5β1 integrin complex through an inverse correlation between CD9 and CD26 expression. Our results also suggest that CD26 and CD9 serve as potential biomarkers as well as promising molecular targets for novel therapeutic approaches in malignant mesothelioma and other malignancies.
Volume 9(1)
Pages e86671
Published 2014
DOI 10.1371/journal.pone.0086671
PII PONE-D-13-38451
PMID 24466195
PMC PMC3900581
MeSH Animals Apoptosis Blotting, Western Cell Membrane / metabolism Cell Movement* Cell Proliferation* Dipeptidyl Peptidase 4 / chemistry Dipeptidyl Peptidase 4 / genetics Dipeptidyl Peptidase 4 / metabolism* Female Flow Cytometry Humans Immunoprecipitation Integrin beta1 / genetics Integrin beta1 / metabolism Lung Neoplasms / metabolism Lung Neoplasms / pathology* Lung Neoplasms / prevention & control* Mesothelioma / metabolism Mesothelioma / pathology* Mesothelioma / prevention & control* Mice Mice, SCID Neoplasm Invasiveness Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Phosphorylation RNA, Messenger / genetics RNA, Small Interfering / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Tetraspanin 29 / antagonists & inhibitors Tetraspanin 29 / genetics Tetraspanin 29 / metabolism* Tumor Cells, Cultured
IF 2.776
Times Cited 21
Human and Animal Cells