Table 1 The diverse functions of cAMP/PKA/CREB in human tumors

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

[57,58,59]

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

[63,64,65]

PKA-Dock180 signaling promotes the development and invasion of glioblastoma

[74, 75]

cAMP–PKA inhibits medulloblastoma by suppressing Hedgehog signaling

[66,67,68]

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, 88,89,90,91,92,93]

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

[97,98,99,100]

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, 119,120,121]

cAMP–PKA may reduce Bcl-2 and survivin expression and increase Bax expression in lymphoma cells, leading to cell apoptosis

[116,117,118]

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]