PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis
| Autor: | Harriet Wikman, Fernanda Machado de Carvalho, Karina N. Gonzalez Herrera, Raghu Kalluri, Ludmilla Thomé Domingos Chinen, Marcia C. Haigis, Joyce T. O’Connell, John M. Asara, Rafael Malagoli Rocha, Klaus Pantel, Valerie S. LeBleu, Aline Santos Damascena |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Blotting Western Mice Nude Breast Neoplasms Oxidative phosphorylation Biology Mitochondrion Oxidative Phosphorylation Metastasis 03 medical and health sciences Oxygen Consumption 0302 clinical medicine Breast cancer Microscopy Electron Transmission Cell Movement Cell Line Tumor Neoplasms medicine Animals Humans Neoplasm Invasiveness Neoplasm Metastasis Transcription factor 030304 developmental biology Regulation of gene expression Mice Inbred BALB C 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction urogenital system Gene Expression Profiling Cell Biology Middle Aged medicine.disease Immunohistochemistry Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mitochondria Cell biology Gene Expression Regulation Neoplastic Mice Inbred C57BL Mitochondrial biogenesis 030220 oncology & carcinogenesis Cancer cell Female RNA Interference Transcription Factors |
| Zdroj: | Nature Cell Biology. 16:992-1003 |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb3039 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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