Preventing cancer metastasis with specific inhibitors of mitochondrial superoxide
(2021) 33rd AICC Annual conference: International Meeting on Cancer Metabolism — Location: Turin, Italy (22.November.2021)
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- Abstract
- Metabolism is a key driver of cancer progression and resistance to treatments. In this study, we further considered that mitochondria within cancer cells could act as metabolic sensors, triggering cancer cell migration, invasion and metastasis. This hypothesis considers that metabolically hostile mircroenvironments could trigger mitochondrial dysfunctions and cell escape from primary tumors. In vitro and in vivo rounds of selection for invasion and metastasis yielded superinvasive and supermetastatic cancer cells that were metabolically compared to the isogenic weakly invasive and weakly metastatic that served as initial material. We report that metastatic progenitor cells produce mitochondrial superoxide, the inhibition of which prevents metastasis. Conversely, weakly metastatic cancer cells manipulated to produce more mitochondrial superoxide gain a metastatic phenotype. Consequently, targeting mitochondrial superoxide with superoxide scavengers such as mitoTEMPO and mitoQ strongly and sometimes fully inhibited the metastatic burden of breast and melanoma cancer models in mice.
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De Miranda Capeloa, T. I., Paolo E Porporato, & Sonveaux, P. (2021). Preventing cancer metastasis with specific inhibitors of mitochondrial superoxide. 33rd AICC Annual conference: International Meeting on Cancer Metabolism, Turin, Italy. https://hdl.handle.net/2078.5/110111