PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation to promote metastasis

By Valerie S. LeBleu, Joyce T. O’Connell, Karina N. Gonzalez Herrera, Harriet Wikman-Kocher, K. Pantel, M. Haigis, F. M. de Carvalho, A. Damascena, L. Chinen, R. Rocha and 2 more. Nature Cell Biology, 2014

1,005 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/25a329fe043d2b350701b7d5500d3f5de9813f8d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Ralph J. Deberardinis
2. M. V. Vander Heiden
3. Bert Vogelstein
4. C. V. Dang
5. Craig B. Thompson
6. Navdeep S. Chandel
7. David M. Sabatini
8. Jason W. Locasale

In Molecular Biology

1. M. V. Vander Heiden
2. Ralph J. Deberardinis
3. Bert Vogelstein
4. Martin A. Nowak
5. Craig B. Thompson
6. C. V. Dang
7. Navdeep S. Chandel
8. David M. Sabatini

In Physiology

1. M. V. Vander Heiden
2. Ralph J. Deberardinis

Citations in the corpus

• Understanding the intersections between metabolism and cancer biology (2017, positive): “In this model, PGC1α was required for cancer cell invasion but not proliferation, perhaps explaining its role in metastasis and dispensability for primary tumor growth.”
• A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity (2015, background): “Their proliferation rate is less than that of cells in the main tumor [75].”
• Targeting cancer stem cell pathways for cancer therapy (2020, background): “395 In addition, the AMPK signaling pathway (adenosine 5′-monophosphate (AMP)-activated protein kinase) is an AMP-dependent protein kinase that is a key molecule in the regulation of bioenergy metabolism and is the core of the study of diabetes and other metabolic-related diseases.”