F2r, also known as the Coagulation Factor II Thrombin Receptor, is an important member of the G-protein-coupled receptor (GPCR) family. It plays a key role in regulating blood clotting through protein hydrolytic cleavage-mediated receptor activation. It is also involved in various biological processes and signaling pathways, such as the Akt and NFκB signaling pathways [1].

In osteoclasts, loss-of-function experiments using F2r-targeted short hairpin RNA (sh-F2r) lentivirus in mouse bone marrow cells (MBMs) showed that F2r knockdown led to increased osteoclast activity, number, and size, as well as promoted bone resorption and F-actin ring formation with increased osteoclast marker gene expression. Conversely, overexpression of F2r blocked osteoclast formation, maturation, and acidification, indicating that F2r negatively regulates osteoclast formation and function by inhibiting the Akt and NFκB signaling pathways [1].

In patients with minor stroke or TIA, the F2R IVSn-14 T allele carriers had a lower rate of recurrent stroke when receiving clopidogrel and aspirin, suggesting the association between F2R polymorphisms and clopidogrel efficacy [2].

In hepatocellular carcinoma, the interaction between GZMA secreted by cytotoxic cells and F2R expressed by tumor cells induced tumor suppression and T cell-mediated killing of tumor cells via the activation of the JAK2/STAT1 signaling pathway, and low expression of GZMA and F2R was correlated with poor prognosis [3].

In stomach adenocarcinoma, knocking down F2R in GC cell lines resulted in slowed proliferation, migration, and invasion, indicating F2R may be a potential biomarker [4].

In conclusion, F2r is crucial in regulating osteoclastogenesis, influencing the efficacy of clopidogrel in stroke patients, playing a role in tumor suppression in hepatocellular carcinoma, and potentially serving as a biomarker in stomach adenocarcinoma. The use of gene-knockout or knockdown models in these studies has provided valuable insights into the functions of F2r in different biological processes and disease conditions.

References:

1. Zhang, Yan, Wang, He, Zhu, Guochun, Qian, Airong, Chen, Wei. 2020. F2r negatively regulates osteoclastogenesis through inhibiting the Akt and NFκB signaling pathways. In International journal of biological sciences, 16, 1629-1639. doi:10.7150/ijbs.41867. https://pubmed.ncbi.nlm.nih.gov/32226307/

2. Pan, Yuesong, Wangqin, Runqi, Li, Hao, Wang, David, Wang, Yongjun. 2020. F2R Polymorphisms and Clopidogrel Efficacy and Safety in Patients With Minor Stroke or TIA. In Neurology, 96, e1-e9. doi:10.1212/WNL.0000000000011078. https://pubmed.ncbi.nlm.nih.gov/33093222/

3. Gao, Yuxue, Xu, Qingguo, Li, Xinqiang, Chen, Dexi, Yang, Tongwang. 2022. Heterogeneity induced GZMA-F2R communication inefficient impairs antitumor immunotherapy of PD-1 mAb through JAK2/STAT1 signal suppression in hepatocellular carcinoma. In Cell death & disease, 13, 213. doi:10.1038/s41419-022-04654-7. https://pubmed.ncbi.nlm.nih.gov/35256589/

4. Wu, Xingwei, Wang, Shengnan, Wang, Chenci, Wu, Chengwei, Zhao, Zhiyong. 2024. Bioinformatics analysis identifies coagulation factor II receptor as a potential biomarker in stomach adenocarcinoma. In Scientific reports, 14, 2468. doi:10.1038/s41598-024-52397-6. https://pubmed.ncbi.nlm.nih.gov/38291086/