Scientists have discovered what supports the cancer activity of stem cells

Researchers led by professors from the Hefei Institute of Physical Sciences of the Chinese Academy of Sciences

discovered for the first time a key factor in maintainingoncogenic activity of glioblastoma stem cells (SCG) — Oct4A (octamer-binding transcription factor 4A). It turned out that ZDHHC17-mediated palmitoylation is necessary to prevent lysosomal degradation of Oct4A, maintain the stability of its protein, and facilitate the formation of complexes between Sox4 (a transcription factor, which is a protein that in humans is encoded by the SOX genome) and Oct4A.

Glioblastoma (GBM) is the most common primaryintracranial tumor in adults with the highest grade of malignancy. Glioblastoma stem cells may be an important cause of radiation and chemotherapy resistance and cancer recurrence. Thus, cell-targeted therapy may become a new strategy for the treatment of malignant glioma.

Oct4 is a member of the transcription familyfactors of the POU family. This gene has several different transcription start sites that can form different mRNA subtypes and be translated into different protein subtypes, participating in the regulation of physiological development. Although it has been found in progressive gliomas, its biological function and transcriptional mechanism have not been fully defined.

In this study, researchers examined the role of the factortranscription of Oct4 in glioma and found a new role for palmitoylation in the function of the splicing variant of this factor in glioma. It turned out that three variants of Oct4 are expressed in different types of brain tumors, and Oct4A is especially important for maintaining tumorigenicity in GSCs. DNA hypomethylation increased the expression of the OCT4 gene, which may be one of the main reasons for the increased expression of stem cell-related genes in recurrent gliomas.

Moreover, scientists have found thatPalmitoylation of Oct4A, mediated by the ZDHHC17 enzyme, is critical to preserve this factor from lysosome degradation, thereby maintaining protein levels in glioma cells in vitro. The researchers also reported that palmitoylated Oct4A interacts with Sox4. Its competitive inhibitors have been tested as potential therapeutic compounds. They negatively affected the ability to self-renewal and oncogenicity of glioblastoma stem cells.

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