Fbxo2, belonging to the F-box proteins (FBPs) family, is a substrate recognition component of the Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex with specificity for high-mannose glycoproteins [2,5]. It is involved in multiple biological processes such as xenophagy, lysophagy, and post-translational regulation of proteins [4,7].

In disease-related studies, FBXO2 knockout in glioma cells conferred a strong survival benefit in orthotopic xenograft mouse models and reduced invasive growth, indicating its role in promoting tumor growth in glioblastoma [1]. In osteosarcoma, FBXO2 knockout by CRISPR-Cas9-based gene editing decreased cell proliferation and colony-forming ability, and impaired the tumorigenicity of cells in nude mice, suggesting it promotes osteosarcoma development through the STAT3 signaling pathway [2]. In papillary thyroid carcinoma, silencing FBXO2 inhibited cell proliferation and promoted apoptosis, and FBXO2 could directly bind to p53 and promote its ubiquitination degradation [3]. In endometrial cancer, FBXO2 knockdown inhibited cell proliferation [6].

In conclusion, Fbxo2 plays a significant role in various biological processes and disease development. Gene knockout studies in mouse models have revealed its pro-tumorigenic functions in multiple cancers, highlighting its potential as a therapeutic target for these diseases.

References:

1. Buehler, Marcel, Yi, Xiao, Ge, Weigang, Guo, Tiannan, Weiss, Tobias. . Quantitative proteomic landscapes of primary and recurrent glioblastoma reveal a protumorigeneic role for FBXO2-dependent glioma-microenvironment interactions. In Neuro-oncology, 25, 290-302. doi:10.1093/neuonc/noac169. https://pubmed.ncbi.nlm.nih.gov/35802605/

2. Zhao, Xunming, Guo, Weichun, Zou, Lixue, Hu, Biao. 2020. FBXO2 modulates STAT3 signaling to regulate proliferation and tumorigenicity of osteosarcoma cells. In Cancer cell international, 20, 245. doi:10.1186/s12935-020-01326-4. https://pubmed.ncbi.nlm.nih.gov/32549792/

3. Guo, Wenke, Ren, Yaoqiang, Qiu, Xinguang. 2024. FBXO2 promotes the progression of papillary thyroid carcinoma through the p53 pathway. In Scientific reports, 14, 22574. doi:10.1038/s41598-024-73455-z. https://pubmed.ncbi.nlm.nih.gov/39343799/

4. Yamada, Akihiro, Hikichi, Miyako, Nozawa, Takashi, Nakagawa, Ichiro. 2021. FBXO2/SCF ubiquitin ligase complex directs xenophagy through recognizing bacterial surface glycan. In EMBO reports, 22, e52584. doi:10.15252/embr.202152584. https://pubmed.ncbi.nlm.nih.gov/34515398/

5. Sun, Xu, Wang, Teng, Guan, Zhang-Rui, Jin, Jian, Hua, Dong. 2017. FBXO2, a novel marker for metastasis in human gastric cancer. In Biochemical and biophysical research communications, 495, 2158-2164. doi:10.1016/j.bbrc.2017.12.097. https://pubmed.ncbi.nlm.nih.gov/29269301/

6. Che, Xiaoxia, Jian, Fangfang, Wang, Ying, Jia, Nan, Feng, Weiwei. 2020. FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway. In Frontiers in cell and developmental biology, 8, 843. doi:10.3389/fcell.2020.00843. https://pubmed.ncbi.nlm.nih.gov/32984335/

7. Liu, Elaine A, Schultz, Mark L, Mochida, Chisaki, Paulson, Henry L, Lieberman, Andrew P. 2020. Fbxo2 mediates clearance of damaged lysosomes and modifies neurodegeneration in the Niemann-Pick C brain. In JCI insight, 5, . doi:10.1172/jci.insight.136676. https://pubmed.ncbi.nlm.nih.gov/32931479/