cAMP-Dependent Signaling and Ovarian Cancer.
Agnieszka KilanowskaAgnieszka ZiółkowskaPiotr StasiakMagdalena Gibas-DornaPublished in: Cells (2022)
cAMP-dependent pathway is one of the most significant signaling cascades in healthy and neoplastic ovarian cells. Working through its major effector proteins-PKA and EPAC-it regulates gene expression and many cellular functions. PKA promotes the phosphorylation of cAMP response element-binding protein (CREB) which mediates gene transcription, cell migration, mitochondrial homeostasis, cell proliferation, and death. EPAC, on the other hand, is involved in cell adhesion, binding, differentiation, and interaction between cell junctions. Ovarian cancer growth and metabolism largely depend on changes in the signal processing of the cAMP-PKA-CREB axis, often associated with neoplastic transformation, metastasis, proliferation, and inhibition of apoptosis. In addition, the intracellular level of cAMP also determines the course of other pathways including AKT, ERK, MAPK, and mTOR, that are hypo- or hyperactivated among patients with ovarian neoplasm. With this review, we summarize the current findings on cAMP signaling in the ovary and its association with carcinogenesis, multiplication, metastasis, and survival of cancer cells. Additionally, we indicate that targeting particular stages of cAMP-dependent processes might provide promising therapeutic opportunities for the effective management of patients with ovarian cancer.
Keyphrases
- binding protein
- cell proliferation
- signaling pathway
- protein kinase
- gene expression
- oxidative stress
- cell cycle arrest
- pi k akt
- cell migration
- induced apoptosis
- dna methylation
- cell adhesion
- transcription factor
- cell death
- single cell
- stem cells
- single molecule
- bone marrow
- high grade
- drug delivery
- immune response
- dna binding