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Warburg Effect Signaling Pathway Luminex Assay (CAT#: STEM-MB-0362-WXH)

Introduction

The Warburg effect is a metabolic phenotype commonly seen in tumors. Even in the presence of sufficient oxygen, cancer cells produce about 60% of their ATP through glycolysis instead of oxidative phosphorylation. The Warburg effect allows dividing cells to use intermediate glucose metabolites to double their biomass and suppress apoptosis. This phenomenon was first discovered by Otto Warburg in the 1920s and was called aerobic glycolysis.




Principle

Several signaling pathways contribute to the Warburg Effect and other metabolic phenotypes of cancer cells. Growth factor stimulation results in signaling through RTKs to activate PI3K/Akt and Ras. Akt promotes glucose transporter activity and stimulates glycolysis through activation of several glycolytic enzymes including hexokinase and phosphofructokinase (PFK). Akt phosphorylation of apoptotic proteins such as Bax makes cancer cells resistant to apoptosis and helps stabilize the outer mitochondrial membrane(OMM) by promoting attachment of mitochondrial hexokinase (mtHK) to the VDAC channel complex. RTK signaling to c-Myc results in transcriptional activation of numerous genes involved in glycolysis and lactate production. The p53 oncogene transactivates TP-53-induced Glycolysis and Apoptosis Regulator (TIGAR) and results in increasedNADPH production by PPS. Signals impacting levels of hypoxia inducible factor (HIF) can increase expression of enzymes such as LDHA to promote lactate production, as well as pyruvate dehydrogenase kinase to inhibit the action of pyruvate dehydrogenase and limit entry of pyruvate into the Krebs Cycle. There is also increasing evidence that availability of metabolic substrates can influence gene expression by affecting epigenetic marks on histones and DNA.

Applications

Study the regulatory mechanism of warburg effect signaling pathway in clinical diseases
Study the influence of various human viruses on the warburg effect signaling pathway
Study the influence of carcinogenic drugs or therapies on the signal pathway of warburg effect

Procedure

• Luminex Multiplex Assay
• Enzyme-linked immunosorbent assay (ELISA)
• Flow cytometry (FACS analysis) technology

Notes

Detectable targets: AKT, c-Myc, ULK1, PFK, PHGDH, Erk1, Erk2, LKB1, LDHA, ANT, VDAC, Bax, UCP2, PDHK, LC3I, PROLC3, ULK, FIP200, VPS15, VPS34, UYRAG, NFκB, RIG-1, TRAF3, IPS-1, ISGF3, MSK2, PI3K, TBK1, Vav, GAS, IRF9, AMBRA1, p38, RIP1, TRAF5, IKK-β, IRS2, MSK1, p65, Tak1, TLR3, Histone-H3, IRF5, MEK3, p38MAPK, SH2, TRAF6, IKK-α, IRS1, MEK6, p50, p53, TRAM, TRIF, IRAK1, ISRE, mTOR, PKR,

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