Copper depletion modulates OXPHOS in SOX2/OCT4+ cancer cells to impair triple negative breast cancer metastasis.
UID: 11078
- Description
- Description from PRIDE:
"Copper serves as a co-factor for a host of metalloenzymes that contribute to malignant progression. The orally bioavailable copper chelating agent tetrathiomolybdate (TM) has been associated with a significant survival benefit in high-risk triple negative breast cancer (TNBC) patients. Despite these promising data, the mechanisms by which copper depletion impacts metastasis are poorly understood and this remains a major barrier to advancing TM to a randomized phase II trial. Here, using two independent TNBC models, we report a discrete subpopulation of highly metastatic SOX2/OCT4+ cells within primary tumors that exhibit elevated intracellular copper levels and marked sensitivity to TM. Global proteomic and metabolomic profiling identified TM-mediated inactivation of Complex IV as the primary metabolic defect in the SOX2/OCT4+ cell population. We identified the AMPK/mTORC1 energy sensor as an important downstream pathway and show that AMPK inhibition rescues TM-mediated loss of invasion. Furthermore, loss of the mitochondria-specific copper chaperone, COX17, restricted copper deficiency to mitochondria and phenocopied TM-mediated alterations. These findings identify a novel copper-metabolism-metastasis axis with potential to enrich patient populations in next-generation therapeutic trials."
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Access via PRIDE
Accession #: PXD027089 - Access Restrictions
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Free to All
- Access Instructions
- All public datasets available in PRIDE Archive in the repository can be accessed via the website by FTP link, Web Service (for programmatic access), and the PRIDE Inspector stand-alone tool.
- Associated Publications
- Equipment Used
- Software Used
- Dataset Format(s)
- Microsoft Excel, RAW
- Dataset Size
- 62.4 GB
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