ADORA2A, also known as adenosine A2a receptor, is a G protein-coupled receptor. It plays significant roles in various biological processes by regulating multiple pathways. For instance, it can rewire proline metabolism via an ERK/MYC/PYCR cascade, which in turn impacts epigenetic reprogramming [1]. It is also involved in the PI3K/AKT pathway, influencing cell proliferation and apoptosis [2].

In genetically engineered mouse models, ablation of Adora2a inhibits the development and progression of neuroendocrine prostate and lung cancers, and prevents the adenocarcinoma-to-neuroendocrine phenotypic transition. Pharmacological blockade of ADORA2A also represses the growth of these cancers in vivo, indicating its potential as a therapeutic target in neuroendocrine malignancies [1]. In addition, polymorphisms in the ADORA2A gene may influence methotrexate treatment response in rheumatoid arthritis, suggesting its importance in drug-related responses [3].

In conclusion, ADORA2A is involved in key biological processes such as metabolism, cell proliferation, and apoptosis. The use of gene-knockout mouse models has revealed its crucial role in neuroendocrine cancers and its potential influence on drug responses in rheumatoid arthritis, highlighting its significance in disease-related research and potential therapeutic applications.

References:

1. Jing, Na, Zhang, Kai, Chen, Xinyu, Gao, Wei-Qiang, Zhu, Helen He. 2023. ADORA2A-driven proline synthesis triggers epigenetic reprogramming in neuroendocrine prostate and lung cancers. In The Journal of clinical investigation, 133, . doi:10.1172/JCI168670. https://pubmed.ncbi.nlm.nih.gov/38099497/

2. Ran, Longyan, Mou, Xiao, Peng, Zhenglin, Sun, Xingwang, Yin, Tao. 2023. ADORA2A promotes proliferation and inhibits apoptosis through PI3K/AKT pathway activation in colorectal carcinoma. In Scientific reports, 13, 19477. doi:10.1038/s41598-023-46521-1. https://pubmed.ncbi.nlm.nih.gov/37945707/

3. Kobold, Nadja, Jenko, Barbara, Tomšič, Matija, Dolžan, Vita, Praprotnik, Sonja. . ADORA2A Polymorphisms Influence Methotrexate Adverse Events in Rheumatoid Arthritis. In The Israel Medical Association journal : IMAJ, 21, 333-338. doi:. https://pubmed.ncbi.nlm.nih.gov/31140226/