Oncotarget

Interview with Dr. Savaskan from the University Hospital Erlangen and BiMECON ENT.

Oncotarget published " PRG3 induces Ras-dependent oncogenic cooperation in gliomas " which reported on the neuronal-associated growth promoting gene PRG3 executing oncogenic cooperation in gliomas.

The researchers 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, undergoes Ras-induced challenges, whereas deletion of the C-terminal domain of PRG3 inhibits Ras.

Thus, the Oncotarget author 's data show that the interference with PRG3 homeostasis amplifies oncogenic properties and fosters the malignancy potential in gliomas.

The Oncotarget author 's data show that the interference with PRG3 homeostasis amplifies oncogenic properties and fosters the malignancy potential in gliomas

Dr. Nicolai E. Savaskan from The Friedrich-Alexander University of Erlangen-N ürnberg (FAU) as well as BiMECON ENT. said, "Malignant gliomas are one of the most common primary brain tumor entities with an annual incidence rate of 5.8 in the USA and in Europe. "

Recently, progress has been made in the characterization of malignant gliomas revealing various heterogeneous genetic lesions with the potential to transform glial progenitor cells and differentiated glial cells into malignant gliomas .

In malignant gliomas PRG3 is expressed in opposing amounts in the way that PRG3 is either elevated or down-regulated compared to non-transformed human specimens.

Analysis of the human expression databases does at least show that a deregulated expression dosage of PRG3 leads to a worse outcome in patients with malignant gliomas.

Deregulated PRG3 expression reduced apoptosis, enhanced proliferation, migration and thus elevated the malignancy of glioma cells.

Further investigations of the underlying signaling pathway revealed that PRG3 interacts with RasGEF1 . Thus, interference with the regulation and homeostasis of PRG3 amplifies malignancy in glioma cells.

The Savaskan Research Team concluded in their Oncotarget Research Paper that the significance of deranged PRG3 levels is reflected by the response rates to therapeutic small molecule inhibitors.

Thus, gliomas with high PRG3 levels are prone to Ras blockers and their tumor growth can be treated with Ras-inhibiting drugs such as salirasib.

Future studies will unravel whether other kinases are affected by PRG3, and if so in which hierarchy the downstream targets affect cell growth.

Altogether, the authors provide evidence that PRG3 acts dosage and context-dependent in the nervous system, and interference with its balanced level can cooperate in oncogenic signaling.

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DOI - https://doi.org/10.18632/oncotarget.8592

Full text - https://www.oncotarget.com/article/8592/text/

Correspondence to - Nicolai E. Savaskan - savaskan@gmx.net, nic.savaskan@gmail.com

Keywords - glioma, PRG3, Ras, oncogenesis, neuronal plasticity

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