RRC ID 18687
Author Niinaka Y, Harada K, Fujimuro M, Oda M, Haga A, Hosoki M, Uzawa N, Arai N, Yamaguchi S, Yamashiro M, Raz A.
Title Silencing of autocrine motility factor induces mesenchymal-to-epithelial transition and suppression of osteosarcoma pulmonary metastasis.
Journal Cancer Res.
Abstract Phosphoglucose isomerase (PGI) is a multifunctional enzyme that functions in glucose metabolism as a glycolytic enzyme catalyzing an interconversion between glucose and fructose inside the cell, while it acts as cytokine outside the cell, with properties that include autocrine motility factor (AMF)-regulating tumor cell motility. Overexpression of AMF/PGI induces epithelial-to-mesenchymal transition with enhanced malignancy. Recent studies have revealed that silencing of AMF/PGI resulted in mesenchymal-to-epithelial transition (MET) of human lung fibrosarcoma cells and breast cancer cells with reduced malignancy. Here, we constructed a hammerhead ribozyme specific against GUC triplet at the position G390 in the human, mouse, and rat AMF/PGI mRNA sequence. Mesenchymal human osteosarcoma MG-63, HS-Os-1, and murine LM8 cells were stably transfected with the ribozyme specific for AMF/PGI. The stable transfectant cells showed effective downregulation of AMF/PGI expression and subsequent abrogation of AMF/PGI secretion, which resulted in morphologic change with reduced growth, motility, and invasion. Silencing of AMF/PGI induced MET, in which upregulation of E-cadherin and cytokeratins, as well as downregulation of vimentin, were noted. The MET guided by AMF/PGI gene silencing induced osteosarcoma MG-63 to terminally differentiate into mature osteoblasts. Furthermore, MET completely suppressed the tumor growth and pulmonary metastasis of LM8 cells in nude mice. Thus, acquisition of malignancy might be completed in part by upregulation of AMF/PGI, and waiver of malignancy might also be controlled by downregulation of AMF/PGI.
Volume 70(22)
Pages 9483-93
Published 2010-11-15
DOI 10.1158/0008-5472.CAN-09-3880
PII 0008-5472.CAN-09-3880
PMID 20978190
PMC PMC2982894
MeSH Animals Base Sequence Blotting, Western Cadherins / genetics Cadherins / metabolism Cell Differentiation Cell Line, Tumor Cell Movement Cell Proliferation Epithelial-Mesenchymal Transition / genetics* Gene Expression Regulation, Neoplastic* Glucose-6-Phosphate Isomerase / genetics* Glucose-6-Phosphate Isomerase / metabolism Humans Keratins / genetics Keratins / metabolism Lung Neoplasms / genetics* Lung Neoplasms / metabolism Lung Neoplasms / secondary Molecular Sequence Data Osteosarcoma / genetics* Osteosarcoma / metabolism Osteosarcoma / pathology RNA, Catalytic / genetics RNA, Catalytic / metabolism Rats Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Nucleic Acid Transfection Tumor Burden Vimentin / genetics Vimentin / metabolism
IF 8.378
Times Cited 35
Human and Animal Cells MG-63 (RCB1890)