PRG3 induces Ras-dependent oncogenic cooperation in gliomas
Fan Z, Bittermann-Rummel P, Yakubov E, Chen D, Broggini T, Sehm T, Hatipoglu Majernik G, Hock S, Schwarz M, Engelhorn T, Dörfler A, Buchfelder M, Eyupoglu IY, Savaskan NE (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 7
Pages Range: 26692-708
Journal Issue: 18
Abstract
Malignant gliomas are one of the most devastating cancers in humans. One characteristic hallmark of malignant gliomas is their cellular heterogeneity with frequent genetic lesions and disturbed gene expression levels conferring selective growth advantage. Here, we report on the neuronal-associated growth promoting gene PRG3 executing oncogenic cooperation in gliomas. We have identified perturbed PRG3 levels in human malignant brain tumors displaying either elevated or down-regulated PRG3 levels compared to non-transformed specimens. Further, imbalanced PRG3 levels in gliomas foster Ras-driven oncogenic amplification with increased proliferation and cell migration although angiogenesis was unaffected. Hence, PRG3 interacts with RasGEF1 (RasGRF1/CDC25), undergoes Ras-induced challenges, whereas deletion of the C-terminal domain of PRG3 (PRG3ΔCT) inhibits Ras. Moreover PRG3 silencing makes gliomas resistant to Ras inhibition. In vivo disequilibrated PRG3 gliomas show aggravated proliferation, invasion, and deteriorate clinical outcome. Thus, our data show that the interference with PRG3 homeostasis amplifies oncogenic properties and foster the malignancy potential in gliomas.
Authors with CRIS profile
Zheng Fan
Department of Neurosurgery
Eduard Yakubov
Medizinische Fakultät
Daishi Chen
Medizinische Fakultät
Tina Sehm
Department of Neurosurgery
Gökce Hatipoglu Majernik
Department of Neurosurgery
Stefan Hock
Medizinische Fakultät
Tobias Martin Engelhorn
Department of Neuroradiology
Arnd Dörfler
Department of Neuroradiology
Michael Buchfelder
Lehrstuhl für Neurochirurgie
Involved external institutions
Germany (DE)How to cite
APA:
Fan, Z., Bittermann-Rummel, P., Yakubov, E., Chen, D., Broggini, T., Sehm, T.,... Savaskan, N.E. (2016). PRG3 induces Ras-dependent oncogenic cooperation in gliomas. Oncotarget, 7(18), 26692-708. https://doi.org/10.18632/oncotarget.8592
MLA:
Fan, Zheng, et al. "PRG3 induces Ras-dependent oncogenic cooperation in gliomas." Oncotarget 7.18 (2016): 26692-708.
BibTeX: Download