Close
  Indian J Med Microbiol
 

Figure 1: Beta-adrenergic signaling pathway in prostatic cancer. When beta-adrenergic receptors on prostate cancer cells are activated by epinephrine or norepinephrine, cellular cAMP level is increased. cAMP level in prostate cancer cells is also elevated by cancer treatments, such as radiation and hormonal therapies. cAMP activates PKA and EPAC. PKA can either directly stimulate or act through PAK4 to increase CREB activity. Activated PKA/CREB axis contributes to several biological processes relevant for cancer progression, such as (1) promoting angiogenesis through induction of VEGF, and repression of TSP1 and PAI2 through inducing HDAC2 and GRK3; (2) promoting NED, at least in part through direct induction of ENO2 as well as GRK3 that in turn elevates neuroendocrine markers in prostate cancer cells; (3) inhibiting apoptosis through CREB-induction of BCL2, and PKA-mediated phosphorylation of BAD (inhibiting) and AKT (activating); (4) together with EPAC, regulating cytoskeletal rearrangement and cellular migration through regulating ROCK activity via RhoA and PAK4. cAMP: cyclic adenosine monophosphate; PKA: protein kinase A; CREB: cAMP response element-binding; VEGF: vascular endothelial growth factor; NED: neuroendocrine differentiation; TSP1: thrombospondin 1; PAI2: plasminogen activator inhibitor-2; HDAC2: histone deacetylase 2; GRK3: G-protein receptor kinase 3; BCL-2: B-cell lymphoma-2; BAD: BCL-2-associated death promoter.

Figure 1: Beta-adrenergic signaling pathway in prostatic cancer. When beta-adrenergic receptors on prostate cancer cells are activated by epinephrine or norepinephrine, cellular cAMP level is increased. cAMP level in prostate cancer cells is also elevated by cancer treatments, such as radiation and hormonal therapies. cAMP activates PKA and EPAC. PKA can either directly stimulate or act through PAK4 to increase CREB activity. Activated PKA/CREB axis contributes to several biological processes relevant for cancer progression, such as (1) promoting angiogenesis through induction of VEGF, and repression of TSP1 and PAI2 through inducing HDAC2 and GRK3; (2) promoting NED, at least in part through direct induction of ENO2 as well as GRK3 that in turn elevates neuroendocrine markers in prostate cancer cells; (3) inhibiting apoptosis through CREB-induction of BCL2, and PKA-mediated phosphorylation of BAD (inhibiting) and AKT (activating); (4) together with EPAC, regulating cytoskeletal rearrangement and cellular migration through regulating ROCK activity via RhoA and PAK4. cAMP: cyclic adenosine monophosphate; PKA: protein kinase A; CREB: cAMP response element-binding; VEGF: vascular endothelial growth factor; NED: neuroendocrine differentiation; TSP1: thrombospondin 1; PAI2: plasminogen activator inhibitor-2; HDAC2: histone deacetylase 2; GRK3: G-protein receptor kinase 3; BCL-2: B-cell lymphoma-2; BAD: BCL-2-associated death promoter.