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

From: Complex roles of cAMP–PKA–CREB signaling in cancer

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 [57,58,59]
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]