Targeting Cancer’s Energy Supply
A groundbreaking study published in Nature reveals that specific modifications in mitochondrial RNA play a crucial role in driving cancer metastasis by enhancing the metabolic plasticity of tumor cells. Researchers from the German Cancer Research Center found that chemical modifications, particularly 5-methylcytosine (m5C) on mitochondrial tRNA, boost mitochondrial protein synthesis, enabling cancer cells to generate more energy for the demanding process of invasion and dissemination. This increased energy production allows cancer cells to adapt to harsh conditions such as low oxygen and nutrient deprivation, which are common during metastatic spread.
The study identified that high levels of these mitochondrial RNA modifications are associated with a gene expression signature predicting poor prognosis and increased metastasis in patients with head and neck cancer. The enzyme NSUN3 is responsible for depositing the m5C modification on mitochondrial tRNA. When NSUN3 was inactivated in cancer cells, the number of metastases was significantly reduced, demonstrating its pivotal role in metastatic progression.
Furthermore, the researchers showed that antibiotics like chloramphenicol or doxycycline, which inhibit mitochondrial protein synthesis, could also block the invasive spread of cancer cells in laboratory models. Importantly, while loss of m5C did not affect the growth of primary tumors, it specifically impaired the metastatic capability by forcing cancer cells to rely on less efficient glycolytic energy pathways. These findings suggest that targeting mitochondrial RNA modifications or the enzymes responsible, such as NSUN3, could be a promising strategy to limit metastasis without harming normal cell viability.
The study provides new insights into how mitochondrial RNA modifications regulate the energy metabolism and adaptability of cancer cells, highlighting a novel mechanism behind metastatic disease and offering potential new avenues for therapeutic intervention.
