American Association for Cancer Research
00085472can131183-sup-fig8.pdf (2.33 MB)

Supplementary Figure 8 from Metastasis Suppressor KISS1 Seems to Reverse the Warburg Effect by Enhancing Mitochondrial Biogenesis

Download (2.33 MB)
journal contribution
posted on 2023-03-30, 22:22 authored by Wen Liu, Benjamin H. Beck, Kedar S. Vaidya, Kevin T. Nash, Kyle P. Feeley, Scott W. Ballinger, Keke M. Pounds, Warren L. Denning, Anne R. Diers, Aimee Landar, Animesh Dhar, Tomoo Iwakuma, Danny R. Welch

PDF file - 2389K, Supplemental Figure 8. C8161.9 cell growth depends upon glucose, but not glutamine. C8161.9Vector (V), C8161.9KFMΔSS, C8161.9KFM and C8161.9KFM/shPGC1α (KFM shP) cells were cultured in 0.1% fetal bovine serum-containing DMEM in the presence (+) or absence (-) of glucose or L-glutamine for 10 days. Representative images of the cell cultures are shown.



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. Cancer Res; 74(3); 954–63. ©2013 AACR.

Usage metrics

    Cancer Research



    Ref. manager