scholarly journals Enzymatic activation of pyruvate kinase increases cytosolic oxaloacetate to inhibit the Warburg effect

2021 ◽  
Author(s):  
Elizabeth K. Wiese ◽  
Sadae Hitosugi ◽  
Sharon T. Loa ◽  
Annapoorna Sreedhar ◽  
Lindsey G. Andres-Beck ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Warburg Effect ◽  
Enzymatic Activation ◽  
The Warburg Effect

scholarly journals Valproic acid Suppresses Breast Cancer Cell Growth Through Triggering Pyruvate Kinase M2 Isoform Mediated Warburg Effect

2021 ◽  
Vol 30 ◽  
pp. 096368972110275
Author(s):  
Zhen Li ◽  
Lina Yang ◽  
Shuai Zhang ◽  
Jiaqi Song ◽  
Huanran Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Valproic Acid ◽  
Cancer Therapy ◽  
Pyruvate Kinase ◽  
Histone Deacetylases ◽  
Warburg Effect ◽  
Broad Class ◽  
Pyruvate Kinase M2 ◽  
Breast Cancer Cell Growth ◽  
The Warburg Effect

Energy metabolism programming is a hallmark of cancer, and serves as a potent target of cancer therapy. Valproic acid (VPA), a broad Class I histone deacetylases (HDACs) inhibitor, has been used as a therapeutic agent for cancer. However, the detail mechanism about the potential role of VPA on the Warburg effect in breast cancer remains unclear. In this study, we highlight that VPA significantly attenuates the Warburg effect by decreasing the expression of pyruvate kinase M2 isoform (PKM2), leading to inhibited cell proliferation and reduced colony formation in breast cancer MCF-7 and MDA-MB-231 cells. Mechanistically, Warburg effect suppression triggered by VPA was mediated by inactivation of ERK1/2 phosphorylation through reduced HDAC1 expression, resulting in suppressing breast cancer growth. In summary, we uncover a novel mechanism of VPA in regulating the Warburg effect which is essential for developing the effective approach in breast cancer therapy.

scholarly journals Pyruvate Kinase M2 Regulates Hif-1α Activity and IL-1β Induction and Is a Critical Determinant of the Warburg Effect in LPS-Activated Macrophages

2015 ◽  
Vol 21 (1) ◽  
pp. 65-80 ◽  
Author(s):  
Eva M. Palsson-McDermott ◽  
Anne M. Curtis ◽  
Gautam Goel ◽  
Mario A.R. Lauterbach ◽  
Frederick J. Sheedy ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Warburg Effect ◽  
Activated Macrophages ◽  
Critical Determinant ◽  
Pyruvate Kinase M2 ◽  
The Warburg Effect

scholarly journals The Warburg Effect Mediator Pyruvate Kinase M2 Expression and Regulation in the Retina

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Raju V. S. Rajala ◽  
Ammaji Rajala ◽  
Christopher Kooker ◽  
Yuhong Wang ◽  
Robert E. Anderson
Keyword(s):  
Pyruvate Kinase ◽  
Warburg Effect ◽  
Pyruvate Kinase M2 ◽  
The Warburg Effect

scholarly journals TSP50 promotes the Warburg effect and hepatocyte proliferation via regulating PKM2 acetylation

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Feng Gao ◽  
Xiaojun Zhang ◽  
Shuyue Wang ◽  
Lihua Zheng ◽  
Ying Sun ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Warburg Effect ◽  
Kinase Activity ◽  
Aerobic Glycolysis ◽  
Tumor Formation ◽  
Metabolic Reprogramming ◽  
Hepatocyte Proliferation ◽  
Pyruvate Kinase Activity ◽  
Hcc Cells ◽  
The Warburg Effect

AbstractMetabolic reprogramming is a hallmark of malignancy. Testes-specific protease 50 (TSP50), a newly identified oncogene, has been shown to play an important role in tumorigenesis. However, its role in tumor cell metabolism remains unclear. To investigate this issue, LC–MS/MS was employed to identify TSP50-binding proteins and pyruvate kinase M2 isoform (PKM2), a known key enzyme of aerobic glycolysis, was identified as a novel binding partner of TSP50. Further studies suggested that TSP50 promoted aerobic glycolysis in HCC cells by maintaining low pyruvate kinase activity of the PKM2. Mechanistically, TSP50 promoted the Warburg effect by increasing PKM2 K433 acetylation level and PKM2 acetylation site (K433R) mutation remarkably abrogated the TSP50-induced aerobic glycolysis, cell proliferation in vitro and tumor formation in vivo. Our findings indicate that TSP50-mediated low PKM2 pyruvate kinase activity is an important determinant for Warburg effect in HCC cells and provide a mechanistic link between TSP50 and tumor metabolism.

scholarly journals ASO-based PKM Splice-switching Therapy Inhibits Hepatocellular Carcinoma Cell Growth

2020 ◽  
Author(s):  
Wai Kit Ma ◽  
Juergen Scharner ◽  
Ana S. H. Costa ◽  
Hyun Yun Jeong ◽  
Michaela Jackson ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mouse Model ◽  
Pyruvate Kinase ◽  
Antisense Oligonucleotides ◽  
Warburg Effect ◽  
Aerobic Glycolysis ◽  
Pyruvate Kinase Activity ◽  
Potential Therapeutic Target ◽  
Splice Isoform ◽  
The Warburg Effect

AbstractThe M2 pyruvate kinase (PKM2) isoform is upregulated in most cancers and plays a crucial role in the Warburg effect, which is characterized by the preference for aerobic glycolysis for energy metabolism. PKM2 is an alternative-splice isoform of the PKM gene, and is a potential therapeutic target. Previously, we developed antisense oligonucleotides (ASOs) that switch PKM splicing from the cancer-associated PKM2 to the PKM1 isoform and induce apoptosis in cultured glioblastoma cells. Here, we explore the potential of ASO-based PKM splice-switching as a targeted therapy for liver cancer. We utilize a lead cEt/DNA ASO, which has a higher potency than MOE modification, to demonstrate that it induces PKM splice-switching and inhibits the growth of cultured hepatocellular-carcinoma (HCC) cells. This PKM isoform switch increases pyruvate-kinase activity and alters glucose metabolism. The lead ASO inhibits tumorigenesis in an orthotopic-xenograft HCC mouse model. Finally, a surrogate mouse-specific ASO induces Pkm splice-switching and inhibits HCC growth, without observable toxicity, in a genetic HCC mouse model.Statement of significanceAntisense oligonucleotides are used to force a change in PKM isoform usage in HCC, reversing the Warburg effect and inhibiting tumorigenesis.

scholarly journals Pyruvate Kinase M2 Regulates Hif-1α Activity and IL-1β Induction and Is a Critical Determinant of the Warburg Effect in LPS-Activated Macrophages

2015 ◽  
Vol 21 (2) ◽  
pp. 347 ◽  
Author(s):  
Eva M. Palsson-McDermott ◽  
Anne M. Curtis ◽  
Gautam Goel ◽  
Mario A.R. Lauterbach ◽  
Frederick J. Sheedy ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Warburg Effect ◽  
Activated Macrophages ◽  
Critical Determinant ◽  
Pyruvate Kinase M2 ◽  
The Warburg Effect
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