The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis

Chand Khanna, Xiaolin Wan, Seuli Bose, Ryan Cassaday, Osarenoma Olomu, Arnulfo Mendoza, Choh Yeung, Richard Gorlick, Stephen M. Hewitt, Lee J. Helman

Research output: Contribution to journalArticle

547 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)182-186
Number of pages5
JournalNature Medicine
Volume10
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

Fingerprint

Osteosarcoma
Cytoskeleton
Neoplasm Metastasis
Membranes
Pediatrics
Neoplasms
Dogs
ezrin
Lung
Phosphorylation
Survival
Neoplasm Genes
Cell membranes
Actin Cytoskeleton
Actins
Tumors
Genes
Chemical activation
Cells
Cell Membrane

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Khanna, C., Wan, X., Bose, S., Cassaday, R., Olomu, O., Mendoza, A., ... Helman, L. J. (2004). The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nature Medicine, 10(2), 182-186. https://doi.org/10.1038/nm982

The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. / Khanna, Chand; Wan, Xiaolin; Bose, Seuli; Cassaday, Ryan; Olomu, Osarenoma; Mendoza, Arnulfo; Yeung, Choh; Gorlick, Richard; Hewitt, Stephen M.; Helman, Lee J.

In: Nature Medicine, Vol. 10, No. 2, 02.2004, p. 182-186.

Research output: Contribution to journalArticle

Khanna, C, Wan, X, Bose, S, Cassaday, R, Olomu, O, Mendoza, A, Yeung, C, Gorlick, R, Hewitt, SM & Helman, LJ 2004, 'The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis', Nature Medicine, vol. 10, no. 2, pp. 182-186. https://doi.org/10.1038/nm982
Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nature Medicine. 2004 Feb;10(2):182-186. https://doi.org/10.1038/nm982
Khanna, Chand ; Wan, Xiaolin ; Bose, Seuli ; Cassaday, Ryan ; Olomu, Osarenoma ; Mendoza, Arnulfo ; Yeung, Choh ; Gorlick, Richard ; Hewitt, Stephen M. ; Helman, Lee J. / The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. In: Nature Medicine. 2004 ; Vol. 10, No. 2. pp. 182-186.
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