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 <p>PDF file - 753K, Supplemental Figure 5. Knocking down PGC1alpha expression abolished KISS1-mediated increase of mitochondria gene expression. The expression of mtTFA, , MT-ND2, MT-RNR2 and nuclear encoded mitochondria genes AIFM2, RHOT1 and TIMM8 in C8161.9Vector (V), C8161.9KFM (P), and C8161.9KFMshPGC1alpha (clones 1-1 and 1-2) were examined by qRT-PCR. Values are mean plus-minus SD of triplicate measurements. P values are based upon a two-sided Student's T-test.</p>
History
ARTICLE 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. Cancer Res; 74(3); 954–63. ©2013 AACR.
