Researchers at the University of Basel took a close look at a signaling pathway present in most organisms and found that it suppresses the formation of specific types of brain tumor. Their results have been published by the journal Cancer Cell.
Gliomas are the most common brain tumors in adults and the prognosis for patients is, in many cases, very bad. Therefore, novel and effective therapies for glioma treatment are needed. In order to develop these, it is crucial to understand the biology of this type of tumor.
Stem cells as potential source of tumors
So far it has been highly debated which brain cells can form gliomas when they acquire gene mutations. However, researchers believe that brain stem cells might be a potential source of this type of cancer. Stem cells in the human brain can generate new nerve cells and, if something goes wrong in this process and uncontrolled proliferation or impaired differentiation occurs, this may lead to the formation of a brain tumor.
A research team led by Professor Verdon Taylor from the Department of Biomedicine at the University of Basel has now studied whether one molecular mechanism that controls normal stem cell maintenance in the brain is hijacked and used by cancer cells during tumor formation.
Active signaling pathway suppresses tumor formation
The researchers studied the so-called Notch pathway. This signaling pathway is central to brain stem cell activity and it has been proposed to – once aberrantly activated – contribute to the growth of gliomas. “In contrast to our expectations, we found that the opposite is the case: when activated, this pathway actually suppresses the formation of some types of glioma”, says Claudio Giachino, first author of the study. Conversely, in some forms of glioma the inactivation of the pathway results in accelerated growth and makes the tumor more aggressive.
Due to these properties, the Notch pathway could, in the future, not only serve as a new therapeutic target but could also be used as a new diagnostic tool in order to get more reliable prognoses for disease progression and patient survival. “Our results demonstrate major differences in the molecular requirements between seemingly similar types of brain tumor and indicate that gliomas must be carefully examined before selecting potentially specific therapeutic interventions in the future”, says Taylor.
About this brain cancer research
Source: Yannik Sprecher – University of Basel Image Credit: The image is credited to Original Research: Full open access research (pdf) for “A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes” by Claudio Giachino, Jean-Louis Boulay, Robert Ivanek, Stefan Pfister, Marcel Kool, and Verdon Taylor in Cancer Cell. Published online December 4 2015 doi:10.1016/j.ccell.2015.10.008
A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes
In the brain, Notch signaling maintains normal neural stem cells, but also brain cancer stem cells, indicating an oncogenic role. Here, we identify an unexpected tumor suppressor function for Notch in forebrain tumor subtypes. Genetic inactivation of RBP-Jk, a key Notch mediator, or Notch1 and Notch2 receptors accelerates PDGF-driven glioma growth in mice. Conversely, genetic activation of the Notch pathway reduces glioma growth and increases survival. In humans, high Notch activity strongly correlates with distinct glioma subtypes, increased patient survival, and lower tumor grade. Additionally, simultaneous nactivation of RBPJk and p53 induces primitive neuroectodermal-like tumors in mice. Hence, Notch signaling cooperates with p53 to restrict cell proliferation and tumor growth in mouse models of human brain tumors.
“A Tumor Suppressor Function for Notch Signaling in Forebrain Tumor Subtypes” by Claudio Giachino, Jean-Louis Boulay, Robert Ivanek, Stefan Pfister, Marcel Kool, and Verdon Taylor in Cancer Cell. Published online December 4 2015 doi:10.1016/j.ccell.2015.10.008