The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis
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- 4 January 2004
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 10 (2), 182-186
- https://doi.org/10.1038/nm982
Abstract
Metastatic cancers, once established, are the primary cause of mortality associated with cancer. Previously, we used a genomic approach to identify metastasis-associated genes in cancer1. From this genomic data, we selected ezrin for further study based on its role in physically and functionally connecting the actin cytoskeleton to the cell membrane2. In a mouse model of osteosarcoma, a highly metastatic pediatric cancer, we found ezrin to be necessary for metastasis. By imaging metastatic cells in the lungs of mice, we showed that ezrin expression provided an early survival advantage for cancer cells that reached the lung. AKT and MAPK phosphorylation and activity were reduced when ezrin protein was suppressed. Ezrin-mediated early metastatic survival was partially dependent on activation of MAPK, but not AKT. To define the relevance of ezrin in the biology of metastasis, beyond the founding mouse model, we examined ezrin expression in dogs that naturally developed osteosarcoma. High ezrin expression in dog tumors was associated with early development of metastases. Consistent with this data, we found a significant association between high ezrin expression and poor outcome in pediatric osteosarcoma patients.Keywords
This publication has 23 references indexed in Scilit:
- Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cellsNature Medicine, 2003
- A molecular signature of metastasis in primary solid tumorsNature Genetics, 2002
- Intravascular Location of Breast Cancer Cells after Spontaneous Metastasis to the LungThe American Journal of Pathology, 2002
- ERM proteins and merlin: integrators at the cell cortexNature Reviews Molecular Cell Biology, 2002
- Signal Pathways Which Promote Invasion and Metastasis: Critical and Distinct Contributions of Extracellular Signal-Regulated Kinase and Ral-Specific Guanine Exchange Factor PathwaysMolecular and Cellular Biology, 2001
- Hierarchy of Merlin and Ezrin N- and C-terminal Domain Interactions in Homo- and Heterotypic Associations and Their Relationship to Binding of Scaffolding Proteins EBP50 and E3KARPJournal of Biological Chemistry, 2001
- Multistep Nature of Metastatic InefficiencyThe American Journal of Pathology, 1998
- Ezrin Is an Effector of Hepatocyte Growth Factor–mediated Migration and Morphogenesis in Epithelial CellsThe Journal of cell biology, 1997
- Ezrin contains cytoskeleton and membrane binding domains accounting for its proposed role as a membrane-cytoskeletal linker.The Journal of cell biology, 1993
- Comparative Aspects of OsteosarcomaPublished by Ovid Technologies (Wolters Kluwer Health) ,1991