The study investigates the role of PGC-1α in mediating mitochondrial biogenesis and oxidative phosphorylation in invasive and metastatic cancer cells. Key findings include: 1. **Circulating Cancer Cells (CCC)**: CCC exhibit enhanced mitochondrial biogenesis and respiration compared to primary tumor cells (PCC) and metastatic lung cells (MCC). This is associated with increased expression of PGC-1α, a transcriptional co-activator that regulates mitochondrial function. 2. **PGC-1α Expression and Mitochondrial Function**: Silencing PGC-1α in cancer cells reduces mitochondrial biogenesis, respiration, and ATP production, while overexpression of PGC-1α enhances these processes. This suggests that PGC-1α is essential for maintaining mitochondrial function in cancer cells. 3. **Invasive and Metastatic Potential**: PGC-1α expression is correlated with the invasive and metastatic capacity of cancer cells. Silencing PGC-1α impairs invasion and metastasis, while overexpression enhances these processes. This indicates that PGC-1α plays a crucial role in facilitating cancer cell migration and dissemination. 4. **Clinical Correlation**: High PGC-1α expression in invasive cancer cells is associated with a higher risk of distant metastases and poor patient outcomes in breast cancer patients. This correlation is observed both in primary tumors and circulating tumor cells (CTCs). 5. **Hypoxia and EMT**: Hypoxia-induced upregulation of PGC-1α is independent of the epithelial-to-mesenchymal transition (EMT) program, suggesting that PGC-1α induction is not mutually exclusive with EMT but functions independently to enhance cancer cell motility and invasion. 6. **Discussion**: The study highlights the importance of PGC-1α-mediated mitochondrial biogenesis and respiration in the metastatic dissemination of cancer cells. These findings suggest that targeting PGC-1α could be a potential therapeutic strategy to impair metastasis. Overall, the research provides new insights into the metabolic requirements of invasive and metastatic cancer cells and identifies PGC-1α as a potential therapeutic target for cancer metastasis.The study investigates the role of PGC-1α in mediating mitochondrial biogenesis and oxidative phosphorylation in invasive and metastatic cancer cells. Key findings include: 1. **Circulating Cancer Cells (CCC)**: CCC exhibit enhanced mitochondrial biogenesis and respiration compared to primary tumor cells (PCC) and metastatic lung cells (MCC). This is associated with increased expression of PGC-1α, a transcriptional co-activator that regulates mitochondrial function. 2. **PGC-1α Expression and Mitochondrial Function**: Silencing PGC-1α in cancer cells reduces mitochondrial biogenesis, respiration, and ATP production, while overexpression of PGC-1α enhances these processes. This suggests that PGC-1α is essential for maintaining mitochondrial function in cancer cells. 3. **Invasive and Metastatic Potential**: PGC-1α expression is correlated with the invasive and metastatic capacity of cancer cells. Silencing PGC-1α impairs invasion and metastasis, while overexpression enhances these processes. This indicates that PGC-1α plays a crucial role in facilitating cancer cell migration and dissemination. 4. **Clinical Correlation**: High PGC-1α expression in invasive cancer cells is associated with a higher risk of distant metastases and poor patient outcomes in breast cancer patients. This correlation is observed both in primary tumors and circulating tumor cells (CTCs). 5. **Hypoxia and EMT**: Hypoxia-induced upregulation of PGC-1α is independent of the epithelial-to-mesenchymal transition (EMT) program, suggesting that PGC-1α induction is not mutually exclusive with EMT but functions independently to enhance cancer cell motility and invasion. 6. **Discussion**: The study highlights the importance of PGC-1α-mediated mitochondrial biogenesis and respiration in the metastatic dissemination of cancer cells. These findings suggest that targeting PGC-1α could be a potential therapeutic strategy to impair metastasis. Overall, the research provides new insights into the metabolic requirements of invasive and metastatic cancer cells and identifies PGC-1α as a potential therapeutic target for cancer metastasis.