Proteomics

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0

Translation proteomics of OSCC CD44/CD36 sorted subpopulations


ABSTRACT: Metabolic flexibility is a common hallmark of aggressive and metastatic cancers. Here, we reveal that dynamic changes in mitochondrial translation rates drive the switch between glycolytic and mitochondrial energy production required for metastasis. We find that loss of 5-methylcytosine (m5C) in mitochondrial tRNAMet is sufficient to repress mitochondrial translation and trigger the switch from oxidative phosphorylation (OXPHOS) to glycolysis. Glycolytic tumour cells form primary tumours but fail to metastasize in an orthotopic mouse model of human oral cancer. Instead, a small subpopulation of non-dividing tumour cells requires high OXPHOS levels for invasion and metastasis. Although this metastasis-initiating metabolic switch is highly dynamic and reversible, we identify a mitochondria-driven gene signature predictive for lymph node metastasis and disease progression. Finally, we demonstrate that pharmacological inhibition of mitochondrial translation blocks metastasis in orthotopic transplants. Together, our results indicate that metastasis-initiating cells can be eradicated by blocking mitochondrial translation.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oral Cancer Cell

SUBMITTER: Kevin Klann  

LAB HEAD: Christian Münch

PROVIDER: PXD021835 | Pride | 2022-06-23

REPOSITORIES: Pride

Dataset's files

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20200728_KKL_HD_F.msf Msf
20200728_KKL_HD_F1.raw Raw
20200728_KKL_HD_F10.raw Raw
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Publications


Aggressive and metastatic cancers show enhanced metabolic plasticity<sup>1</sup>, but the precise underlying mechanisms of this remain unclear. Here we show how two NOP2/Sun RNA methyltransferase 3 (NSUN3)-dependent RNA modifications-5-methylcytosine (m<sup>5</sup>C) and its derivative 5-formylcytosine (f<sup>5</sup>C) (refs.<sup>2-4</sup>)-drive the translation of mitochondrial mRNA to power metastasis. Translation of mitochondrially encoded subunits of the oxidative phosphorylation complex dep  ...[more]

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