PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis
Copyright policy )PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis
Cancer cells can divert metabolites into anabolic pathways to support their rapid proliferation and to accumulate the cellular building blocks required for tumour growth. However, the specific bioenergetic profile of invasive and metastatic cancer cells is unknown. Here we report that migratory/invasive cancer cells specifically favour mitochondrial respiration and increased ATP production. Invasive cancer cells use the transcription coactivator peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PPARGC1A, also known as PGC-1α) to enhance oxidative phosphorylation, mitochondrial biogenesis and the oxygen consumption rate. Clinical analysis of human invasive breast cancers revealed a strong correlation between PGC-1α expression in invasive cancer cells and the formation of distant metastases. Silencing of PGC-1α in cancer cells suspended their invasive potential and attenuated metastasis without affecting proliferation, primary tumour growth or the epithelial-to-mesenchymal program. Inherent genetics of cancer cells can determine the transcriptome framework associated with invasion and metastasis, and mitochondrial biogenesis and respiration induced by PGC-1α are also essential for functional motility of cancer cells and metastasis.
- The University of Texas MD Anderson Cancer Center United States
- Harvard University United States
- Beth Israel Deaconess Medical Center United States
- Harvard Medical School United States
- Universität Hamburg Germany
Male, Mice, Inbred BALB C, Gene Expression Profiling, Blotting, Western, Mice, Nude, Breast Neoplasms, Middle Aged, Immunohistochemistry, Mitochondria, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Cell Movement, Cell Line, Tumor, Neoplasms, Animals, Humans, Female, Neoplasm Invasiveness, Neoplasm Metastasis
Male, Mice, Inbred BALB C, Gene Expression Profiling, Blotting, Western, Mice, Nude, Breast Neoplasms, Middle Aged, Immunohistochemistry, Mitochondria, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Cell Movement, Cell Line, Tumor, Neoplasms, Animals, Humans, Female, Neoplasm Invasiveness, Neoplasm Metastasis
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