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The roles of respiration and ATP production in tumorigenesis and metastasis

Year:
2020
Duration:
42 months
Approved budget:
$1,197,497.55
Researchers:
Professor Michael Berridge
,
Dr David O'Sullivan
,
Associate Professor Patries Herst
,
Dr David Eccles
Health issue:
Cancer (oncology)
Proposal type:
Project
Lay summary
The ability of cancer cells to alter the balance between mitochondrial and glycolytic ATP production allows them to survive and metastasize under adverse conditions. We recently discovered that metastatic breast cancer and melanoma cells that lack mitochondrial DNA and therefore are unable to respire or produce mitochondrial ATP do not form tumours unless they acquire mitochondria with mitochondrial DNA from normal cells. We showed that the presence of mitochondrial DNA is required for the expression of a set of nuclear immune response genes. We also showed that respiration is required for tumour growth, to provide building blocks for nucleic acid synthesis, but mitochondrial ATP generation is not necessary. We will investigate the drivers of mitochondrial acquisition in metastatic tumour models and explore the role of mitochondrial DNA in controlling tumour immune responses. In addition, we will determine whether or not mitochondrial ATP production is required for metastasis.