%0 Journal Article
%T Adenylate cyclase 4 suppresses malignant progression of lung adenocarcinoma through interaction with protein kinase C beta
%A Wang, Jieyang
%A Zheng, Chaojing
%A Shen, Wei
%A Chen, Qianshun
%A Lin, Yuyu
%A Huang, Shuwei
%A Gao, Lei
%A Huang, Chen
%J Translational Cancer Research
%D 2026
%B 2026
%9 
%! Adenylate cyclase 4 suppresses malignant progression of lung adenocarcinoma through interaction with protein kinase C beta
%K 
%X Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and remains a leading cause of cancer-related mortality. However, the functional role and regulatory mechanism of adenylate cyclase 4 (ADCY4) in LUAD progression are not fully understood. Therefore, this study aimed to systematically explore the expression pattern, prognostic value, and biological function of ADCY4 in LUAD, and to elucidate its potential regulatory mechanism through interaction with protein kinase C beta (PRKCB).Methods: Integrated analyses of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA)-LUAD datasets were conducted to identify key dysregulated genes and signaling pathways in LUAD. The expression pattern and prognostic significance of ADCY4 were evaluated. Gain-of-function experiments and a series of in vitro assays were performed to assess the biological effects of ADCY4 on LUAD cells. Protein-protein interactions (PPIs) were explored using bioinformatics prediction and co-immunoprecipitation (Co-IP) assays.Results: ADCY4 was significantly downregulated in LUAD tissues and cell lines, and decreased ADCY4 expression was associated with poor patient prognosis. Functional assays demonstrated that ADCY4 overexpression markedly suppressed LUAD cell proliferation, migration, and invasion. Mechanistically, ADCY4 directly interacted with PRKCB and positively regulated its expression. Rescue experiments demonstrated that PRKCB mediates the tumor-suppressive effects of ADCY4. Importantly, in vivo xenograft assays further confirmed that ADCY4 suppresses tumor growth through PRKCB-dependent mechanisms.Conclusions: Our findings identify ADCY4 as a novel tumor suppressor in LUAD that inhibits malignant progression through PRKCB-dependent signaling. ADCY4 may serve as a promising prognostic biomarker and potential therapeutic target for LUAD.
%U https://tcr.amegroups.org/article/view/122226
%V 15
%N 7
%P 559
%@ 2219-6803