Upregulation of adenylate cyclase 3 (ADCY3) increases the tumorigenic potential of cells by activating the CREB pathway

• DOI: 10.18632/oncotarget.1324
• Publication Date: 2015-09-16T21:45:54Z
• Authors: Seung-Hyun Hong; Sung-Ho Goh; Sang Jin Lee; Jung-Ah Hwang; Jieun Lee; Il-Ju Choi; Hyehyun Seo; Jong-Hoon Park; Hiromu Suzuki; Eiichiro Yamamoto; In-Hoo Kim; Jin Sook Jeong; Mi Ha Ju; Dong-Hee Lee; Yeon-Su Lee
• Keywords: Cyclic adenosine monophosphate; Demethylating agent; Ectopic expression

Adenylate cyclase 3 (ADCY3) is a widely expressed membrane-associated protein in human tissues, which catalyzes the formation of cyclic adenosine-3',5'-monophosphate (cAMP). However, our transcriptome analysis gastric cancer tissue samples (NCBI GEO GSE30727) revealed that ADCY3 expression was specifically altered samples. Here we investigated tumor-promoting effects overexpression and confirmed significant correlation between upregulation Lauren's intestinal-type cancers. increased cell migration, invasion, proliferation, clonogenicity HEK293 cells; conversely, silencing SNU-216 cells reduced these phenotypes. Interestingly, both mRNA level activity matrix metalloproteinase 2 (MMP2) MMP9 by increasing levels cAMP phosphorylated cAMP-responsive element-binding (CREB). Consistent with findings, treatment kinase A (PKA) inhibitor decreased MMP2 ADCY3-overexpressing cells. Knockdown stable shRNA suppressed tumor growth xenograft model. Thus, may exert its via cAMP/PKA/CREB pathway. Additionally, bisulfite sequencing promoter region gene hypermethylation CpG sites, 5-Aza-2'-deoxycytidine (5-Aza-dC)-induced demethylation. Our study first to report an association as well tumorigenic potentials. In addition, demonstrate regulated through epigenetic mechanism. Further on mechanism tumorigenesis will provide basis new molecular target cancer.