Mitochondrial Protein Cox7b Is a Metabolic Sensor Driving Brain-Specific Metastasis of Human Breast Cancer Cells
(2022) Cancers — Vol. 14, n° 18, p. 4371 [1-24] (2022)
Files
130MarineCox7b.pdf
Open Access - Adobe PDF
- 2.78 MB
Details
- Authors
Blackman, Marine 
De Miranda Capeloa, Tania Isabel Zampieri, Luca Daskalopoulos, Evangelos-Panagiotis
- Abstract
- (en) Distant metastases are detrimental for cancer patients, but the increasingly early detection of tumors offers a chance for metastasis prevention. Importantly, cancers do not metastasize randomly: depending on the type of cancer, metastatic progenitor cells have a predilection for well-defined organs. This has been theorized by Stephen Paget, who proposed the "seed-and-soil hypothesis", according to which metastatic colonization occurs only when the needs of a given metastatic progenitor cell (the seed) match with the resources provided by a given organ (the soil). Here, we propose to explore the seed-and-soil hypothesis in the context of cancer metabolism, thus hypothesizing that metastatic progenitor cells must be capable of detecting the availability of metabolic resources in order to home in a secondary organ. If true, it would imply the existence of metabolic sensors. Using human triple-negative MDA-MB-231 breast cancer cells and two independent brain-seeking variants as models, we report that cyclooxygenase 7b (Cox7b), a structural component of Complex IV of the mitochondrial electron transport chain, belongs to a probably larger family of proteins responsible for breast cancer brain tropism in mice. For metastasis prevention therapy, this proof-of-principle study opens a quest for the identification of therapeutically targetable metabolic sensors that drive cancer organotropism.
- Affiliations
Citations
Blackman, M., De Miranda Capeloa, T. I., Rondeau, J., Zampieri, L., Benyahia, Z., Van de Velde, J., Fransolet, M., Daskalopoulos, E.-P., Michiels, C., Beauloye, C., & Sonveaux, P. (2022). Mitochondrial Protein Cox7b Is a Metabolic Sensor Driving Brain-Specific Metastasis of Human Breast Cancer Cells. Cancers, 14(18), 4371 [1-24]. https://doi.org/10.3390/cancers14184371 (Original work published 2022)