Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin

X. Wan, S. Y. Kim, L. M. Guenther, A. Mendoza, J. Briggs, C. Yeung, D. Currier, H. Zhang, C. MacKall, W. J. Li, R. S. Tuan, A. T. Deyrup, C. Khanna, Lee J. Helman

Research output: Contribution to journalArticle

Abstract

The development of pulmonary metastasis is the major cause of death in osteosarcoma, and its molecular basis is poorly understood. In this study, we show that Β4 integrin is highly expressed in human osteosarcoma cell lines and tumor samples. Furthermore, highly metastatic MNNG-HOS cells have increased levels of Β4 integrin. Suppression of Β4 integrin expression by shRNA and disruption of Β4 integrin function by transfection of dominant-negative Β4 integrin was sufficient to revert this highly metastatic phenotype in the MNNG-HOS model without significantly affecting primary tumor growth. These findings suggest a role for Β4 integrin expression in the metastatic phenotype in human osteosarcoma cells. In addition, we identified a previously uncharacterized interaction between Β4 integrin and ezrin, a membrane-cytoskeletal linker protein that is implicated in the metastatic behavior of osteosarcoma. The Β4 integrin-ezrin interaction appears to be critical for maintenance of Β4 integrin expression. These data begin to integrate ezrin and Β4 integrin expression into a model of action for the mechanism of osteosarcoma metastases.

Original languageEnglish (US)
Pages (from-to)3401-3411
Number of pages11
JournalOncogene
Volume28
Issue number38
DOIs
StatePublished - Sep 24 2009
Externally publishedYes

Fingerprint

Integrin beta4
Osteosarcoma
Integrins
Neoplasm Metastasis
Methylnitronitrosoguanidine
Plakins
ezrin
Phenotype
Tumor Cell Line
Small Interfering RNA

Keywords

  • B4 integrin
  • Ezrin
  • Interaction
  • Metastases
  • Osteosarcoma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Wan, X., Kim, S. Y., Guenther, L. M., Mendoza, A., Briggs, J., Yeung, C., ... Helman, L. J. (2009). Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin. Oncogene, 28(38), 3401-3411. https://doi.org/10.1038/onc.2009.206

Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin. / Wan, X.; Kim, S. Y.; Guenther, L. M.; Mendoza, A.; Briggs, J.; Yeung, C.; Currier, D.; Zhang, H.; MacKall, C.; Li, W. J.; Tuan, R. S.; Deyrup, A. T.; Khanna, C.; Helman, Lee J.

In: Oncogene, Vol. 28, No. 38, 24.09.2009, p. 3401-3411.

Research output: Contribution to journalArticle

Wan, X, Kim, SY, Guenther, LM, Mendoza, A, Briggs, J, Yeung, C, Currier, D, Zhang, H, MacKall, C, Li, WJ, Tuan, RS, Deyrup, AT, Khanna, C & Helman, LJ 2009, 'Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin', Oncogene, vol. 28, no. 38, pp. 3401-3411. https://doi.org/10.1038/onc.2009.206
Wan X, Kim SY, Guenther LM, Mendoza A, Briggs J, Yeung C et al. Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin. Oncogene. 2009 Sep 24;28(38):3401-3411. https://doi.org/10.1038/onc.2009.206
Wan, X. ; Kim, S. Y. ; Guenther, L. M. ; Mendoza, A. ; Briggs, J. ; Yeung, C. ; Currier, D. ; Zhang, H. ; MacKall, C. ; Li, W. J. ; Tuan, R. S. ; Deyrup, A. T. ; Khanna, C. ; Helman, Lee J. / Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin. In: Oncogene. 2009 ; Vol. 28, No. 38. pp. 3401-3411.
@article{85d200d5a0044f7787ea7af2b4a03cf1,
title = "Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin",
abstract = "The development of pulmonary metastasis is the major cause of death in osteosarcoma, and its molecular basis is poorly understood. In this study, we show that Β4 integrin is highly expressed in human osteosarcoma cell lines and tumor samples. Furthermore, highly metastatic MNNG-HOS cells have increased levels of Β4 integrin. Suppression of Β4 integrin expression by shRNA and disruption of Β4 integrin function by transfection of dominant-negative Β4 integrin was sufficient to revert this highly metastatic phenotype in the MNNG-HOS model without significantly affecting primary tumor growth. These findings suggest a role for Β4 integrin expression in the metastatic phenotype in human osteosarcoma cells. In addition, we identified a previously uncharacterized interaction between Β4 integrin and ezrin, a membrane-cytoskeletal linker protein that is implicated in the metastatic behavior of osteosarcoma. The Β4 integrin-ezrin interaction appears to be critical for maintenance of Β4 integrin expression. These data begin to integrate ezrin and Β4 integrin expression into a model of action for the mechanism of osteosarcoma metastases.",
keywords = "B4 integrin, Ezrin, Interaction, Metastases, Osteosarcoma",
author = "X. Wan and Kim, {S. Y.} and Guenther, {L. M.} and A. Mendoza and J. Briggs and C. Yeung and D. Currier and H. Zhang and C. MacKall and Li, {W. J.} and Tuan, {R. S.} and Deyrup, {A. T.} and C. Khanna and Helman, {Lee J.}",
year = "2009",
month = "9",
day = "24",
doi = "10.1038/onc.2009.206",
language = "English (US)",
volume = "28",
pages = "3401--3411",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "38",

}

TY - JOUR

T1 - Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin

AU - Wan, X.

AU - Kim, S. Y.

AU - Guenther, L. M.

AU - Mendoza, A.

AU - Briggs, J.

AU - Yeung, C.

AU - Currier, D.

AU - Zhang, H.

AU - MacKall, C.

AU - Li, W. J.

AU - Tuan, R. S.

AU - Deyrup, A. T.

AU - Khanna, C.

AU - Helman, Lee J.

PY - 2009/9/24

Y1 - 2009/9/24

N2 - The development of pulmonary metastasis is the major cause of death in osteosarcoma, and its molecular basis is poorly understood. In this study, we show that Β4 integrin is highly expressed in human osteosarcoma cell lines and tumor samples. Furthermore, highly metastatic MNNG-HOS cells have increased levels of Β4 integrin. Suppression of Β4 integrin expression by shRNA and disruption of Β4 integrin function by transfection of dominant-negative Β4 integrin was sufficient to revert this highly metastatic phenotype in the MNNG-HOS model without significantly affecting primary tumor growth. These findings suggest a role for Β4 integrin expression in the metastatic phenotype in human osteosarcoma cells. In addition, we identified a previously uncharacterized interaction between Β4 integrin and ezrin, a membrane-cytoskeletal linker protein that is implicated in the metastatic behavior of osteosarcoma. The Β4 integrin-ezrin interaction appears to be critical for maintenance of Β4 integrin expression. These data begin to integrate ezrin and Β4 integrin expression into a model of action for the mechanism of osteosarcoma metastases.

AB - The development of pulmonary metastasis is the major cause of death in osteosarcoma, and its molecular basis is poorly understood. In this study, we show that Β4 integrin is highly expressed in human osteosarcoma cell lines and tumor samples. Furthermore, highly metastatic MNNG-HOS cells have increased levels of Β4 integrin. Suppression of Β4 integrin expression by shRNA and disruption of Β4 integrin function by transfection of dominant-negative Β4 integrin was sufficient to revert this highly metastatic phenotype in the MNNG-HOS model without significantly affecting primary tumor growth. These findings suggest a role for Β4 integrin expression in the metastatic phenotype in human osteosarcoma cells. In addition, we identified a previously uncharacterized interaction between Β4 integrin and ezrin, a membrane-cytoskeletal linker protein that is implicated in the metastatic behavior of osteosarcoma. The Β4 integrin-ezrin interaction appears to be critical for maintenance of Β4 integrin expression. These data begin to integrate ezrin and Β4 integrin expression into a model of action for the mechanism of osteosarcoma metastases.

KW - B4 integrin

KW - Ezrin

KW - Interaction

KW - Metastases

KW - Osteosarcoma

UR - http://www.scopus.com/inward/record.url?scp=70349440966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349440966&partnerID=8YFLogxK

U2 - 10.1038/onc.2009.206

DO - 10.1038/onc.2009.206

M3 - Article

VL - 28

SP - 3401

EP - 3411

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 38

ER -