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Supplementary Figure 6 from Metastasis Suppressor KISS1 Seems to Reverse the Warburg Effect by Enhancing Mitochondrial Biogenesis

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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 - 6436K, Supplemental Figure 6. PGC1alpha is essential for KISS1 suppression of invasion and migration. MelJuSoKFM cells were transfected with a control shRNA or an shRNA targeting PGC1α followed by evaluation of transwell invasion (left panel) and migration using a scratch assay (right panel). Representative images for migrating and invading cells are shown. Values are mean plus-minus SD of triplicate samples. P-values are based upon a two-sided Student's T-test; ***, p<0.001.</p>

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    DOI - Is supplement to Metastasis Suppressor KISS1 Seems to Reverse the Warburg Effect by Enhancing Mitochondrial Biogenesis

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.

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    Cancer Research

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    Breast CancerOncogenes & Tumor SuppressorsSuppressors of metastasisProgression, Invasion & MetastasisMetastasisSkin Cancers

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