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. 2019 Nov 18;9:1248. doi: 10.3389/fonc.2019.01248

Figure 6.

Figure 6

Canonical WNT/β-catenin pathway, Warburg glycolysis, and cancer. Schema of the canonical WNT pathway under aerobic glycolysis in cancer. In the presence of WNT ligands (“on state”), β-catenin accumulates in the cytosol and then translocates to the nucleus to bind TCF-LEF co-transcription factors. This induces the WNT-response gene transcription (CYCLIN D1, cMYC, PDK, MCT-1, fibronectin, etc). Glucose itself activates the canonical WNT pathway. PDK inhibits the PDH complex in mitochondria. Thus, pyruvate cannot be fully converted into acetyl-CoA and cannot enter the TCA cycle. cMYC activates LDH-A which converts cytosolic pyruvate into lactate. MCT-1 favors lactate extrusion out of the cytosol which favors angiogenesis. cMYC increases glutamine entry into both the cytosol and mitochondria. cMYC-induced glutamine enhances aspartate and nucleotide synthesis.