Back to Search
Start Over
Metastasis suppressor KISS1 seems to reverse the Warburg effect by enhancing mitochondrial biogenesis.
- Source :
-
Cancer research [Cancer Res] 2014 Feb 01; Vol. 74 (3), pp. 954-63. Date of Electronic Publication: 2013 Dec 18. - Publication Year :
- 2014
-
Abstract
- Cancer cells tend to utilize aerobic glycolysis even under normoxic conditions, commonly called the "Warburg effect." Aerobic glycolysis often directly correlates with malignancy, but its purpose, if any, in metastasis remains unclear. When wild-type KISS1 metastasis suppressor is expressed, aerobic glycolysis decreases and oxidative phosphorylation predominates. However, when KISS1 is missing the secretion signal peptide (ΔSS), invasion and metastasis are no longer suppressed and cells continue to metabolize using aerobic glycolysis. KISS1-expressing cells have 30% to 50% more mitochondrial mass than ΔSS-expressing cells, which are accompanied by correspondingly increased mitochondrial gene expression and higher expression of PGC1α, a master coactivator that regulates mitochondrial mass and metabolism. PGC1α-mediated downstream pathways (i.e., fatty acid synthesis and β-oxidation) are differentially regulated by KISS1, apparently reliant upon direct KISS1 interaction with NRF1, a major transcription factor involved in mitochondrial biogenesis. Since the downstream effects could be reversed using short hairpin RNA to KISS1 or PGC1α, these data appear to directly connect changes in mitochondria mass, cellular glucose metabolism, and metastasis.
- Subjects :
- Animals
Cell Line, Tumor
Disease Models, Animal
Extracellular Space metabolism
Female
Gene Expression
Glucose metabolism
Glycolysis
Humans
Hydrogen-Ion Concentration
Kisspeptins metabolism
Lactic Acid metabolism
Mice
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasms pathology
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Transcription Factors genetics
Transcription Factors metabolism
Kisspeptins genetics
Mitochondria genetics
Mitochondria metabolism
Neoplasms genetics
Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 74
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 24351292
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-13-1183