The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis

被引：551

作者：

Khanna C. ^{[1
]}

Wan X. ^{[1
]}

Bose S. ^{[1
]}

Cassaday R. ^{[1
]}

Olomu O. ^{[1
]}

Mendoza A. ^{[1
]}

Yeung C. ^{[1
]}

Gorlick R. ^{[3
]}

Hewitt S.M. ^{[2
]}

Helman L.J. ^{[1
]}

机构：

[1] Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda

[2] Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda

[3] Mem. Sloan Kettering Cancer Center, New York

来源：

Nature Medicine | 2004年 / 10卷 / 2期

关键词：

D O I：

10.1038/nm982

中图分类号：

学科分类号：

摘要：

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 cancer. 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 membrane. 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.

引用

页码：182 / 186

页数：4

共 27 条

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