Ral overactivation in malignant peripheral nerve sheath tumors

Vidya Bodempudi, Farnaz Yamoutpoor, Weihong Pan, Arkadiusz Z. Dudek, Tuba Esfandyari, Mark Piedra, Dusica Babovick-Vuksanovic, Richard A. Woo, Victor F. Mautner, Lan Kluwe, D. Wade Clapp, George H. DeVries, Stacey L. Thomas, Andreas Kurtz, Luis F. Parada, Faris Farassati

Research output: Contribution to journalArticle

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Abstract

Ras leads an important signaling pathway that is deregulated in neurofibromatosis type 1 and malignant peripheral nerve sheath tumor (MPNST). In this study, we show that overactivation of Ras and many of its downstream effectors occurred in only a fraction of MPNST cell lines. RalA, however, was overactivated in all MPNST cells and tumor samples compared to nontransformed Schwann cells. Silencing Ral or inhibiting it with a dominant-negative Ral (Ral S28N) caused a significant reduction in proliferation, invasiveness, and in vivo tumorigenicity of MPNST cells. Silencing Ral also reduced the expression of epithelial mesenchymal transition markers. Expression of the NF1-GTPase-related domain (NF1-GRD) diminished the levels of Ral activation, implicating a role for neurofibromin in regulating RalA activation. NF1-GRD treatment caused a significant decrease in proliferation, invasiveness, and cell cycle progression, but cell death increased. We propose Ral overactivation as a novel cell signaling abnormality in MPNST that leads to important biological outcomes with translational ramifications.

Original languageEnglish (US)
Pages (from-to)3964-3974
Number of pages11
JournalMolecular and Cellular Biology
Volume29
Issue number14
DOIs
StatePublished - Jul 2009

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Neurilemmoma
GTP Phosphohydrolases
Neurofibromin 1
Neurofibromatosis 1
Epithelial-Mesenchymal Transition
Schwann Cells
Tumor Cell Line
Cell Cycle
Cell Death
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Bodempudi, V., Yamoutpoor, F., Pan, W., Dudek, A. Z., Esfandyari, T., Piedra, M., ... Farassati, F. (2009). Ral overactivation in malignant peripheral nerve sheath tumors. Molecular and Cellular Biology, 29(14), 3964-3974. https://doi.org/10.1128/MCB.01153-08

Ral overactivation in malignant peripheral nerve sheath tumors. / Bodempudi, Vidya; Yamoutpoor, Farnaz; Pan, Weihong; Dudek, Arkadiusz Z.; Esfandyari, Tuba; Piedra, Mark; Babovick-Vuksanovic, Dusica; Woo, Richard A.; Mautner, Victor F.; Kluwe, Lan; Clapp, D. Wade; DeVries, George H.; Thomas, Stacey L.; Kurtz, Andreas; Parada, Luis F.; Farassati, Faris.

In: Molecular and Cellular Biology, Vol. 29, No. 14, 07.2009, p. 3964-3974.

Research output: Contribution to journalArticle

Bodempudi, V, Yamoutpoor, F, Pan, W, Dudek, AZ, Esfandyari, T, Piedra, M, Babovick-Vuksanovic, D, Woo, RA, Mautner, VF, Kluwe, L, Clapp, DW, DeVries, GH, Thomas, SL, Kurtz, A, Parada, LF & Farassati, F 2009, 'Ral overactivation in malignant peripheral nerve sheath tumors', Molecular and Cellular Biology, vol. 29, no. 14, pp. 3964-3974. https://doi.org/10.1128/MCB.01153-08
Bodempudi V, Yamoutpoor F, Pan W, Dudek AZ, Esfandyari T, Piedra M et al. Ral overactivation in malignant peripheral nerve sheath tumors. Molecular and Cellular Biology. 2009 Jul;29(14):3964-3974. https://doi.org/10.1128/MCB.01153-08
Bodempudi, Vidya ; Yamoutpoor, Farnaz ; Pan, Weihong ; Dudek, Arkadiusz Z. ; Esfandyari, Tuba ; Piedra, Mark ; Babovick-Vuksanovic, Dusica ; Woo, Richard A. ; Mautner, Victor F. ; Kluwe, Lan ; Clapp, D. Wade ; DeVries, George H. ; Thomas, Stacey L. ; Kurtz, Andreas ; Parada, Luis F. ; Farassati, Faris. / Ral overactivation in malignant peripheral nerve sheath tumors. In: Molecular and Cellular Biology. 2009 ; Vol. 29, No. 14. pp. 3964-3974.
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