Metabolic requirements of the metastasis-initiating tumour cell population using oral squamous cell carcinoma (OSCC) as a model system

Here, we reveal that mitochondrial tRNA methylation is essential for efficient mitochondrial translation to dynamically shape cancer metabolism required for metastasis. Using oral squamous cell carcinoma (OSCC, SCC25 from ATCCR CRL-168TM and patient-derived cell lines with the names VDH01, VDH15) as a model system, we reveal the metabolic requirements of the metastasis-initiating tumour cell population. Only non-dividing tumour cells with high mitochondrial translation rates can invade and disseminate from primary tumours. Thus, inhibition of mitochondrial translation either through deletion of NSUN3 or through pharmacological inhibitors both block metastasis in orthotopic transplantation assays. Together, our study demonstrates that mitochondrial translation controls the metabolic reprogramming required for invasion and dissemination from the primary tumour.EGA study EGAS00001004765