Adrb2, also known as the beta-2 adrenergic receptor, is a crucial component of the adrenergic signaling pathway. It plays a significant role in regulating various physiological processes and is involved in multiple disease-related pathways. Activation of Adrb2 has been associated with anti-apoptotic mechanisms in cancer cells, and it also participates in pathways related to cell proliferation, autophagy, and metastasis [1,2,3]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying Adrb2's function in vivo.

In multiple cancer types, research has revealed important roles of Adrb2. In prostate cancer, Adrb2 signaling contributes to tumor progression and therapy resistance through anti-apoptotic mechanisms, and understanding its signaling in the context of other pathways can help identify patients who may benefit from propranolol therapy [1]. In hepatocellular carcinoma (HCC), Adrb2 signaling promotes cancer cell proliferation, survival, and sorafenib resistance by inhibiting autophagic degradation of HIF1α, and its inhibition can enhance anti-tumor activity of sorafenib [2]. In gastric cancer, stress-hormone induced activation of Adrb2 signaling pathway is crucial for cancer progression and metastasis, and Adrb2 antagonists can suppress these processes by inhibiting relevant MAPK pathways and transcription factors [3]. In gastrointestinal stromal tumor (GIST), high Adrb2 expression is associated with risk level, tumor size, mitotic count, and metastasis, and it promotes GIST cell proliferation, migration, invasion, and apoptosis by enhancing the ETV1-c-KIT signaling [5]. Additionally, in chimeric antigen receptor (CAR)-T cell therapy against prostate cancer, downregulating Adrb2 in CAR-T cells via RNA interference improves their anti-tumor functions [4].

In conclusion, Adrb2 is a key player in the adrenergic signaling pathway with significant implications in cancer biology. Model-based research, especially KO/CKO mouse models, could potentially further elucidate its role in cancer and other diseases. Understanding Adrb2's function provides insights into potential therapeutic strategies, such as the use of beta-blockers or targeting Adrb2-related pathways in treating various cancers.

References:

1. Kulik, George. 2019. ADRB2-Targeting Therapies for Prostate Cancer. In Cancers, 11, . doi:10.3390/cancers11030358. https://pubmed.ncbi.nlm.nih.gov/30871232/

2. Wu, Fu-Quan, Fang, Tian, Yu, Le-Xing, Yang, Wen, Wang, Hong-Yang. 2016. ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α. In Journal of hepatology, 65, 314-24. doi:10.1016/j.jhep.2016.04.019. https://pubmed.ncbi.nlm.nih.gov/27154061/

3. Zhang, Xuan, Zhang, Yi, He, Zhongyuan, Zhang, Lu, Xu, Zekuan. 2019. Chronic stress promotes gastric cancer progression and metastasis: an essential role for ADRB2. In Cell death & disease, 10, 788. doi:10.1038/s41419-019-2030-2. https://pubmed.ncbi.nlm.nih.gov/31624248/

4. Ajmal, Iqra, Farooq, Muhammad Asad, Duan, Yixin, Du, Bingtan, Jiang, Wenzheng. 2024. Intrinsic ADRB2 inhibition improves CAR-T cell therapy efficacy against prostate cancer. In Molecular therapy : the journal of the American Society of Gene Therapy, 32, 3539-3557. doi:10.1016/j.ymthe.2024.08.028. https://pubmed.ncbi.nlm.nih.gov/39228124/

5. Chen, Sijun, Wu, Feijing, Zhang, Jiaxuan, Zhou, Xiaorong, Zhi, Xiaofei. 2023. ADRB2 Regulates the Proliferation and Metastasis of Gastrointestinal Stromal Tumor Cells by Enhancing the ETV1-c-KIT Signaling. In Journal of oncology, 2023, 6413796. doi:10.1155/2023/6413796. https://pubmed.ncbi.nlm.nih.gov/36778918/