PGC-1α promotes metastasis by enhancing mitochondrial biogenesis and oxidative phosphorylation in invasive cancer cells. The study shows that migratory/invasive cancer cells prefer mitochondrial respiration and increased ATP production. Invasive cancer cells use PGC-1α to enhance oxidative phosphorylation, mitochondrial biogenesis, and oxygen consumption. Clinical analysis of human invasive breast cancers revealed a strong correlation between PGC-1α expression in invasive cancer cells and formation of distant metastases. Silencing PGC-1α in cancer cells reduced their invasive potential and metastasis without affecting proliferation, primary tumor growth, or EMT program. PGC-1α is enriched in circulating tumor cells (CTCs) and is associated with enhanced mitochondrial biogenesis and respiration. PGC-1α expression was highest among genes promoting mitochondrial biogenesis. PGC-1α expression in CTCs was significantly up-regulated compared to primary tumor cells (PCCs). PGC-1α expression in CTCs was associated with increased mitochondrial DNA content, ATP levels, and mitochondrial respiration. PGC-1α expression facilitated mitochondrial biogenesis and invasion of cancer cells. PGC-1α suppression reduced invasion and metastasis, while over-expression enhanced invasion and restored invasive properties. PGC-1α expression was associated with distant metastasis and poor prognosis in patients with invasive breast cancer. PGC-1α expression was detected in CTCs from metastatic breast cancer patients and was negative for leukocyte marker CD45. PGC-1α expression was correlated with formation of distant metastases in patients with invasive breast cancer. PGC-1α expression was associated with enhanced mitochondrial respiration and oxidative phosphorylation, which are essential for cancer cell motility and metastasis. PGC-1α expression was also associated with EMT program and mesenchymal phenotype. PGC-1α expression was essential for intravasation of cancer cells into the circulation. PGC-1α expression was associated with enhanced migratory and invasive properties of cancer cells. PGC-1α expression was associated with poor prognosis in patients with invasive breast cancer. PGC-1α expression was associated with increased mitochondrial respiration and oxidative phosphorylation, which are critical for cancer cell survival and metastasis. PGC-1α expression was associated with enhanced mitochondrial biogenesis and respiration, which are essential for cancer cell motility and metastasis. PGC-1α expression was associated with EMT program and mesenchymal phenotype. PGC-1α expression was associated with enhanced migratory and invasive properties of cancer cells. PGC-1α expression was associated with poor prognosis in patients with invasive breast cancer. PGC-1α expression was associated with increased mitochondrial respiration and oxidative phosphorylation, which are critical for cancer cell survival and metastasis. PGC-1α expression was associated with enhanced mitochondrial biogenesis and respiration, which arePGC-1α promotes metastasis by enhancing mitochondrial biogenesis and oxidative phosphorylation in invasive cancer cells. The study shows that migratory/invasive cancer cells prefer mitochondrial respiration and increased ATP production. Invasive cancer cells use PGC-1α to enhance oxidative phosphorylation, mitochondrial biogenesis, and oxygen consumption. Clinical analysis of human invasive breast cancers revealed a strong correlation between PGC-1α expression in invasive cancer cells and formation of distant metastases. Silencing PGC-1α in cancer cells reduced their invasive potential and metastasis without affecting proliferation, primary tumor growth, or EMT program. PGC-1α is enriched in circulating tumor cells (CTCs) and is associated with enhanced mitochondrial biogenesis and respiration. PGC-1α expression was highest among genes promoting mitochondrial biogenesis. PGC-1α expression in CTCs was significantly up-regulated compared to primary tumor cells (PCCs). PGC-1α expression in CTCs was associated with increased mitochondrial DNA content, ATP levels, and mitochondrial respiration. PGC-1α expression facilitated mitochondrial biogenesis and invasion of cancer cells. PGC-1α suppression reduced invasion and metastasis, while over-expression enhanced invasion and restored invasive properties. PGC-1α expression was associated with distant metastasis and poor prognosis in patients with invasive breast cancer. PGC-1α expression was detected in CTCs from metastatic breast cancer patients and was negative for leukocyte marker CD45. PGC-1α expression was correlated with formation of distant metastases in patients with invasive breast cancer. PGC-1α expression was associated with enhanced mitochondrial respiration and oxidative phosphorylation, which are essential for cancer cell motility and metastasis. PGC-1α expression was also associated with EMT program and mesenchymal phenotype. PGC-1α expression was essential for intravasation of cancer cells into the circulation. PGC-1α expression was associated with enhanced migratory and invasive properties of cancer cells. PGC-1α expression was associated with poor prognosis in patients with invasive breast cancer. PGC-1α expression was associated with increased mitochondrial respiration and oxidative phosphorylation, which are critical for cancer cell survival and metastasis. PGC-1α expression was associated with enhanced mitochondrial biogenesis and respiration, which are essential for cancer cell motility and metastasis. PGC-1α expression was associated with EMT program and mesenchymal phenotype. PGC-1α expression was associated with enhanced migratory and invasive properties of cancer cells. PGC-1α expression was associated with poor prognosis in patients with invasive breast cancer. PGC-1α expression was associated with increased mitochondrial respiration and oxidative phosphorylation, which are critical for cancer cell survival and metastasis. PGC-1α expression was associated with enhanced mitochondrial biogenesis and respiration, which are