| First Author | Bodempudi V | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 14 | Pages | 3964-74 |
| PubMed ID | 19414599 | Mgi Jnum | J:150147 |
| Mgi Id | MGI:3849792 | Doi | 10.1128/MCB.01153-08 |
| Citation | Bodempudi V, et al. (2009) Ral overactivation in malignant peripheral nerve sheath tumors. Mol Cell Biol 29(14):3964-74 |
| abstractText | 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. |
