Table 1.
The diverse functions of cAMP/PKA/CREB in human tumors
| Cancer type | cAMP/PKA/CREB functions | References |
|---|---|---|
| HCC | DNAJB1–PRKACA gene fusion in FL-HCC patients promote tumor progression | [54, 55] |
| Overexpression of PRKACA in BAP1-mutated HCC promotes tumor progression | [56] | |
| HBVx promotes liver carcinogenesis through CREB-miR-3188, CREB-YAP and Erk-CREB pathways | [57–59] | |
| cAMP analogues and PDE inhibitors inhibits HepG2 cell growth by down-regulating cyclin A and up-regulating p21/p27/p53 | [52, 61] | |
| Brain tumor | cAMP inhibits glioblastoma cell growth by up-regulating p21/p27 and PKA/ Epac1-Rap1 signaling | [63–65] |
| PKA-Dock180 signaling promotes the development and invasion of glioblastoma | [74, 75] | |
| cAMP–PKA inhibits medulloblastoma by suppressing Hedgehog signaling | [66–68] | |
| CREB promotes glioma progression through down-regulating PTEN | [72, 76] | |
| Lung cancer | cAMP can down-regulate SIRT6 expression and inhibit NSCLC cells apoptosis | [78, 79] |
| PKA promotes hypoxia-induced epithelial-mesenchymal transformation, cell migration and invasion of lung cancer cells | [84] | |
| PKA induces PP2A phosphorylation and AP1, thereby increases radiotherapy-induced lung cancer cell apoptosis | [86, 87] | |
| Prostate cancer | PKA can up-regulate AR signaling and the neuroendocrine differentiation of prostate cancer, leading to androgen-independence, resistance to androgen deprivation therapy and cancer progression | [81, 88–93] |
| Epithelial ovarian cancer | PKA promotes extracellular matrix degradation and reduces the intensity of tight junction in epithelial ovarian cancer cells by phosphorylating claudin-3, leading to tumor invasion and metastasis | [97–100] |
| Breast cancer | PKA promotes the growth and metastasis of triple negative breast cancer cells through GSK3-β-catenin pathway | [104] |
| PKA induces ERα Ser305 phosphorylation, tamoxifen resistance and ER-positive breast cancer progression | [106, 107] | |
| PKA promotes trastuzumab resistance in Her-2 positive breast cancer | [108] | |
| Leukemia and lymphoma | cAMP promotes TLR signaling and apoptosis of chronic lymphocytic leukemia (CLL) cells | [112, 113, 119–121] |
| cAMP–PKA may reduce Bcl-2 and survivin expression and increase Bax expression in lymphoma cells, leading to cell apoptosis | [116–118] | |
| Overexpression of CREB in AML patients is associated with poor prognosis. Overexpression of CREB can promote AML cells proliferation by up-regulating cyclin A1 expression | [122, 123] |