ADCY4 inhibits cAMP-induced growth of breast cancer by inactivating FAK/AKT and ERK signaling but is frequently silenced by DNA methylation.

ABSTRACT: Local increases in cyclic adenosine monophosphate (cAMP) caused by specific adenylyl cyclases (ACs) can selectively modulate related proteins. AC-selective drugs have an advantage in side effect control, and the specific AC may finally be considered as a therapeutic target. We show that adenylyl cyclase 4 (ADCY4), which is silenced by DNA methylation and is critical for breast cancer (BC) patient survival, plays essential roles in anti-tumor effects in BC cells. DNA methyltransferase inhibitor and histone deacetylase inhibitor can restore ADCY4 mRNA expression in ADCY4-silenced BC cells. ADCY4 directly affects BC cell proliferation, apoptosis, invasion, and metastasis. Mechanistically, ADCY4 converts ATP to cAMP and activates cAMP/PKA signaling, leading to a decrease in the phosphorylation

SUBMITTER: Pan G 

PROVIDER: S-EPMC12217726 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature