Research News

METTL8 links mt-tRNA m3C modification to the HIF1α/RTK/Akt axis to sustain GBM stemness and tumorigenicity

Glioblastoma is the most common and lethal form of adult brain cancer. The presence of cancer stem cells (so-called glioma stem cells) within the tumour, makes it difficult to eradicate glioblastoma as these cells can persist indefinitely and resist conventional therapies. In this paper, A/Prof Derrick Ong and his team discovered that a protein named methyltransferase 8 (METTL8) is involved in the 3-methylcytosine modification of specific mitochondrial-tRNAs, which indirectly promotes mitochondrial translation and respiration. Surprisingly, the METTL8-mediated mitochondrial respiration influences the hypoxia-regulatory cancer pathway, which helps maintain glioblastoma hallmarks. This finding has important translational value because it may explain why drugs targeting the hypoxia pathway fail to eradicate this cancer clinically. Targeting the METTL8 protein could be a new therapeutic strategy to eliminate glioblastoma.

Read more: https://www.nature.com/articles/s41419-024-06718-2

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