Adora1, also known as Adenosine A1 Receptor, is a crucial receptor that binds to adenosine and is involved in various physiological processes. Adenosine signaling via Adora1 participates in regulating multiple pathways, which are important for maintaining normal cellular functions and physiological homeostasis [1-5]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying Adora1's functions.

In cancer research, tumor Adora1 deletion in human melanoma cell lines suppresses cell growth in vitro and tumor development in immune-deficient xenografts, but it upregulates PD-L1 levels, leading to tumor immune evasion and reduced anti-tumor immunity in immune-competent mouse models [1]. In nasopharyngeal carcinoma (NPC), Adora1 overexpression promotes cell proliferation, invasion, and migration through the PI3K/AKT/GSK-3β/β-catenin signaling pathway, while its knockdown inhibits murine xenograft tumor growth [2]. Similar oncogenic roles of Adora1 via the PI3K/AKT pathway are also seen in hepatocellular carcinoma, where its overexpression increases cell proliferation and invasion, and knockdown inhibits growth and sensitizes to chemotherapy [3]. In papillary thyroid carcinoma, Adora1 is overexpressed, positively correlated with lymph node metastasis and pathological stage, and has diagnostic and prognostic value [4].

In conclusion, Adora1 plays essential roles in multiple biological processes, especially in the context of cancer, where its manipulation can significantly impact tumor growth, immune evasion, and metastasis. The use of Adora1 KO or CKO mouse models has been instrumental in uncovering these functions, providing insights into potential therapeutic strategies for cancer treatment. Additionally, Adora1 is involved in non-cancer conditions like sepsis-associated acute kidney injury, where its activation protects against injury by inhibiting pyroptosis [5].

References:

1. Liu, Hong, Kuang, Xinwei, Zhang, Yongchang, Hung, Mien-Chie, Chen, Xiang. . ADORA1 Inhibition Promotes Tumor Immune Evasion by Regulating the ATF3-PD-L1 Axis. In Cancer cell, 37, 324-339.e8. doi:10.1016/j.ccell.2020.02.006. https://pubmed.ncbi.nlm.nih.gov/32183950/

2. Pan, Suming, Liang, Sixian, Wang, Xianyan. 2021. ADORA1 promotes nasopharyngeal carcinoma cell progression through regulation of PI3K/AKT/GSK-3β/β-catenin signaling. In Life sciences, 278, 119581. doi:10.1016/j.lfs.2021.119581. https://pubmed.ncbi.nlm.nih.gov/33961854/

3. Ni, Sheng, Wei, Qian, Yang, Li. 2020. ADORA1 Promotes Hepatocellular Carcinoma Progression via PI3K/AKT Pathway. In OncoTargets and therapy, 13, 12409-12419. doi:10.2147/OTT.S272621. https://pubmed.ncbi.nlm.nih.gov/33293832/

4. Lin, Xu, Wang, Zhi-Yong, Xue, Gang, Wu, Jing-Fang, Zhang, Geng. 2021. ADORA1 is a diagnostic-related biomarker and correlated with immune infiltrates in papillary thyroid carcinoma. In Journal of Cancer, 12, 3997-4010. doi:10.7150/jca.50743. https://pubmed.ncbi.nlm.nih.gov/34093805/

5. He, Wei, Pan, Kaixin, Xiao, Chenggen. 2025. Activation ADORA1 protects against sepsis-associated acute kidney injury by inhibiting pyroptosis. In Tissue & cell, 95, 102849. doi:10.1016/j.tice.2025.102849. https://pubmed.ncbi.nlm.nih.gov/40090281/