Ws2, also known as WD repeat and SOCS box containing protein 2, is an E3 ubiquitin ligase. It is involved in multiple biological processes and disease-related pathways. It can bind to certain proteins and promote their ubiquitination and degradation, thus participating in the regulation of signaling pathways such as IGFBP3-AKT-mTOR, Wnt/β-catenin, and NF-κB, which are crucial for cell growth, apoptosis, and tumorigenesis [1,2,3].

In hepatocellular carcinoma (HCC), high expression of WSB2 degrades wild-type p53 through promoting K48-linked p53 polyubiquitination at specific sites, leading to the activation of the IGFBP3-AKT-mTOR pathway, driving HCC tumorigenesis and lung metastasis [1].

In Xuanwei lung cancer, WSB2 was frequently up-regulated, and its knockdown reduced cell viability, invasion, and epithelial-mesenchymal transition (EMT), while inducing apoptosis and cell cycle arrest, as it activated the Wnt/β-catenin pathway [2].

In melanoma cells, high levels of WSB2 were associated with clinicopathological features, and its knockdown inhibited cell proliferation, cycle progression, and migration, likely through down-regulating c-Myc, β-catenin, p-Rb, CDK4, and Cyclin D3 [4].

In conclusion, WSB2 is an important E3 ubiquitin ligase that plays key roles in the development of multiple cancers, including HCC, Xuanwei lung cancer, and melanoma, mainly by regulating important signaling pathways. Studies on WSB2 using knockdown or knockout models in these cancer-related contexts help to understand its function in tumorigenesis, providing potential new targets for cancer treatment.