The study, recently published in the journal Communications Biology, identified a new mechanism mediated by the KANSL2 protein, which is involved
in the development and growth of a highly malignant brain tumor known as glioblastoma.
Glioblastoma is one of the most aggressive brain tumors, affecting approximately 3 out of every 100,000 people. It is characterized by rapid growth and a tendency to recur even after intensive treatment, making it an exceptionally difficult disease to treat. Understanding how this uncontrolled growth is sustained and the mechanisms regulating glioblastoma’s cellular identity are primary challenges for the “Tumor Stem Cells and Cellular Plasticity” research group, led by Dr. Carolina Perez-Castro.
The KANSL2 protein—identified years ago by Perez-Castro’s group alongside colleagues from FLENI—is elevated in glioblastoma cells. It plays a significant role in tumor formation by maintaining stem cell properties and cancer cell heterogeneity. This new study published in Communications Biology, conducted with local and international collaborators, demonstrates that KANSL2 also promotes ribosome production in glioblastoma cells through epigenetic regulation, thereby fueling tumor growth.
The Cell’s Production Factory
To grow and divide, all cells must produce proteins. To achieve this, they rely on fundamental structures called ribosomes, which function as tiny factories within the cell.
In cancer cells, this system is often hyper-activated: more ribosomes lead to more proteins and a greater capacity to multiply. “Producing proteins is vital for cell multiplication. While KANSL2 regulates factors contributing to the aggressiveness of these tumors, this paper demonstrates that one of its tumorigenic functions is regulating ribosome biogenesis and, consequently, protein production capacity”, explains Perez-Castro.
“We observed that KANSL2 moves to the nucleolus—crucial for ribosome production and assembly—in a coordinated and dynamic manner with the cell cycle to stimulate ribosomal RNA production”, says Agustín Morellato, a postdoc in the group.
“We also found that KANSL2 facilitates this process, in part, by making the factors necessary for ribosome production more accessible”, comments Nicolás Budnik, the study’s lead author.
Consequently, the KANSL2 protein activates the genes required to produce more proteins and sustain cell proliferation. “As confirmation of this discovery, we saw that when the levels of this protein are decreased in a cell, it produces fewer ribosomes; when increased, it produces more”, Budnik adds.
This finding explains how glioblastoma sustains its massive growth capacity: by boosting ribosome production and, with it, protein synthesis.
Ultimately, the research reveals that KANSL2 acts as a key regulator of the glioblastoma “production factory”, linking epigenetic regulation with the tumor cells’ ability to grow, survive, and regulate their identity. In a type of cancer where therapeutic options remain limited, understanding these mechanisms is a fundamental step toward identifying potential therapeutic targets.