Table 1 Regulators of glycolysis associated with thyroid cancer cells growth
Regulators | Effects in glycolysis | Effects in TC growth | Downstream molecules | Participation pathway | Mechanism | |
|---|---|---|---|---|---|---|
Negative regulators | PTEN | Negative | Negative | HIF-1, VEGF, PCNA | PI3K/PTEN/AKT, PI3K-AKT-mTOR | Inhibit GLUT1 expression and glucose uptake in TC, downregulate PI3K-AKT-mTOR pathway and affect glucose metabolism |
P53 | Negative | Negative | AMPK, GLUT1,3,4, PGM, TSC2, RRAD | PI3K-AKT-mTOR, caspase pathway | Shorten glucose uptake and promote mitochondrial oxidation, so as to resist Warburg effect, which also leads to cell cycle arrest and apoptotic cell death | |
Iodide | Negative | Negative | GLUT1 | Oxidation pathway, rate-limiting glucose-facilitated transport system | Inhibit TSH induced stimulation of glucose transport, reduce the number of available carrier sites and inhibit cell growth | |
BRAFV600E | Negative | Negative | GLUT1 | RAF/MEK/ERK | Initiate the glycolytic table associated with GLUT1 overexpression and inhibit mitochondrial respiration in thyroid cells | |
Positive regulators | HIF-1 | Positive | Positive | GLUT1, PDK, PKM2, HKII | PI3K/AKT | Enhance glycolysis, increase GLUTs expression, and promote tumor growth |
PI3K/AKT | Positive | Positive | GLUT1, HKII, PDK1 | PI3K/AKT | Promote cell carcinogenesis and increase glycolytic flux | |
TSH | Positive | Positive | mTOR | PI3K.AKT, RAS/MAPK | Promote thymocyte proliferation and thyroid proliferation | |
c-Myc | Positive | Positive | GLUT1, LDHA, PK, PKM2, MCTs | APC, miR-222-3p/HIPK2/ERK | Promote anaerobic glycolysis, tumor growth and cell proliferation | |
AMPK | Positive | Negative | HIF-1α, mTOR | AMPK/AKT, AMPT/mTOR | Regulate glycolysis and control cell growth, apoptosis and survival | |
LDHA | Positive | Positive | STAT3 | JAK/STAT | Promote the conversion of pyruvate to lactic acid, so as to promote the glycolysis process and tumor growth | |
PD-1 | Positive | Positive | SHP2, RAS | SHP2/RAS/MAPK, RAS-MAPK-ERS | Promote the proliferation and vitality of thyroid cancer cells | |