Ral overactivation in malignant peripheral nerve sheath tumors.
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Ral overactivation in malignant peripheral nerve sheath tumors. / Vidya, Bodempudi; Yamoutpoor, Farnaz; Pan, Weihong; Dudek, Arkadiusz Z; Esfandyari, Tuba; Piedra, Mark; Babovick-Vuksanovic, Dusica; Woo, Richard A; Mautner, Viktor Felix; Kluwe, Lan; Vries, De; George, H; Thomas, Stacey L; Kurtz, Andreas; Parada, Luis F; Farassati, Faris.
in: MOL CELL BIOL, Jahrgang 29, Nr. 14, 14, 2009, S. 3964-3974.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Ral overactivation in malignant peripheral nerve sheath tumors.
AU - Vidya, Bodempudi
AU - Yamoutpoor, Farnaz
AU - Pan, Weihong
AU - Dudek, Arkadiusz Z
AU - Esfandyari, Tuba
AU - Piedra, Mark
AU - Babovick-Vuksanovic, Dusica
AU - Woo, Richard A
AU - Mautner, Viktor Felix
AU - Kluwe, Lan
AU - Vries, De
AU - George, H
AU - Thomas, Stacey L
AU - Kurtz, Andreas
AU - Parada, Luis F
AU - Farassati, Faris
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 29
SP - 3964
EP - 3974
JO - MOL CELL BIOL
JF - MOL CELL BIOL
SN - 0270-7306
IS - 14
M1 - 14
ER -
