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Mitochondrial oxidative transport is inhibited by NDUFA4L2 to promote primary tumor escape [RNA-Seq]

GSE296702 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2025/05/12 Platform GPL24247
Summary
Metastases cause most cancer deaths and reflect cellular transitions from epithelial to mesenchymal states (EMT) that enable primary tumor escape to seeding and growth at metastatic sites. Rare cancer-driving mutations that disrupt mitochondrial oxidative metabolism (OxPhos) can promote EMT, yet molecular mechanisms that more broadly link metabolism to metastases are uncertain. Analyses of clear cell renal cell carcinoma (RCC) cells identified the hypoxia-induced mitochondrial electron transport inhibitor, NDUFA4L2, as highly enriched in cancer cells with EMT signatures. NDUFA4L2 suppressed OxPhos, altering levels of metabolites that govern chromatin accessibility of EMT-related loci. NDUFA4L2 specifically promoted cell escape from primary orthotopic RCC rather than colonization to drive lung metastasis. These results demonstrate OxPhos inhibition by NDUFA4L2 is essential for RCC cells undergoing EMT to escape primary tumors.
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Direct links to NCBI, no account and no request form: the whole study as GSE296702_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1260557 and SRA study SRP583978. Searching any of these in the dataset finder brings you back here.

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