Scientists have discovered what supports the cancer activity of stem cells

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

discovered for the first time a key factor in maintainingoncogenic activity of glioblastoma stem cells (GSC) - Oct4A (octamer-binding transcription factor 4A). It turned out that palmitoylation mediated by the ZDHHC17 enzyme is necessary to prevent lysosomal degradation of Oct4A, maintain the stability of its protein and facilitate the formation of complexes between Sox4 (transcription factor , which is a protein encoded by the human genome SOX) 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 relapse. Cell-targeted therapy may therefore 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, which can form different subtypes of mRNA and be translated into different subtypes of proteins, participating in the regulation of physiological development. Although it has been found in progressive gliomas, its biological function and transcription mechanism are not were completely defined.

In this study, researchers examined the role of the factorOct4 transcription in glioma and discovered a novel role for palmitoylation in splice variant function of this factor in glioma. Three Oct4 variants were found to be expressed in different types of brain tumors, and Oct4A was particularly important for maintaining tumorigenicity in GSCs. DNA hypomethylation increased OCT4 gene expression, which may be one of the main reasons for the increased expression of stem cell-related genes in recurrent gliomas.

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

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