Table 2.
Role of phosphodiesterases on glioblastoma.
| Phosphodiesterase | Gene Chromosome | Substrate | Main Function | Participation in GBM | Ref. |
|---|---|---|---|---|---|
| PDE1 |
PDE1A, B, C 2q32.1, 12q13.2, 7q14.3 |
cAMP and cGMP | Promotes cell proliferation and migration | PDE1C is overexpressed on GBM | [29,30,31,32] |
| PDE2 |
PDE2A 11q13.4 |
cAMP and cGMP | Regulates endothelial permeability and proliferation and nNOS expression. | PDE2A is overexpressed in low grade glioma | [33,34] |
| PDE3 |
PDE3A, B 12q12.2, 11p15.2 |
cAMP and cGMP | Smooth muscle contraction, insulin signaling, blood vessel formation, and antiapoptotic and anti-inflammatory pathways | N. D. | [35,36,37] |
| PDE4 |
PDE4A, B, C, D 19p13.2, 1p31.3, 19p13.11, 5p11.2-q12.1 |
cAMP | Promotes blood vessel formation, monocyte and macrophage activation, and antiapoptotic and anti-inflammatory pathways | PDE4 promotes the tumor growth Hypermethylation of the PDE4C promoter is associated with high malignant grade and reduced overall survival |
[36,38,39,40,41] |
| PDE5 |
PDE5A 4q26 |
cGMP | Regulates cell signaling | PDE5 is overexpression correlates with longer overall survival, and its inhibition induces an invasive phenotype of GBM | [7,42] |
| PDE6 |
PDE6A, B, C 5q32, 4p16.3, 10q24 |
cGMP | Participates in rod and cone photoreceptor function | N. D. | [43,44,45] |
| PDE7 |
PDE7A, B 8q13, 6q23-24 |
cAMP | Modulation of T-cell proliferation | PDE7B overexpression induces tumor growth | [46,47,48,49] |
| PDE8 |
PDE8A, B 15q25.3, 15q13.3 |
cAMP | Controls T cells and breast cancer cells motility | PDE8A expression correlates with an increased overall survival | [50,51,52,53] |
| PDE9 |
PDE9A 21q22.3 |
cGMP | Participates in synaptic plasticity and cognitive function | N. D. | [54,55] |
| PDE10 |
PDE10A 6q26 |
cAMP and cGMP | Regulates intracellular signaling and controls striatal gene expression | PDE10A is deleted on GBM tissue | [56,57,58] |
| PDE11 |
PDE11A 2q31.2 |
cAMP and cGMP | Contributes to sperm development | N. D. | [59] |
GBM, glioblastoma; Ref., reference; PDE, phosphodiesterase; cAMP, cyclic Adenosine Monophosphate; cGMP, cyclic Guanosine Monophosphate; nNOS, neural Nitric Oxide Synthetase; N. D., no data. Cursive for gene names.