Ubxn2a, a ubiquitin-like protein, plays crucial roles in multiple biological processes. It is involved in regulating protein turnover within key signaling pathways, most notably the mTORC2 pathway, which is significant in tumor progression. Ubxn2a also has implications in the degradation of specific oncoproteins, and its functions are vital in understanding cancer-related biological mechanisms [1-3]. Genetic models, such as mouse models, have been instrumental in studying Ubxn2a's functions.

In murine models, haploinsufficiency of Ubxn2a significantly increases colon tumorigenesis, indicating its role as a tumor suppressor [1]. Ubxn2a targets Rictor, a key component of the mTORC2 complex, for 26S proteasomal degradation, reducing AKT phosphorylation downstream of the mTORC2 pathway, which is essential for cell migration. CRC patients with high Ubxn2a levels have better survival, and high-grade CRC tissues show decreased Ubxn2a protein expression. Additionally, in vitro studies show that overexpression of Ubxn2a decreases Rictor protein levels, and veratridine-induced upregulation of Ubxn2a suppresses mTORC2 downstream pathway and cancer stem cells essential for tumor metastasis [1,2].

In conclusion, Ubxn2a is a significant regulator in biological processes, especially in the context of cancer. Mouse models, particularly those with Ubxn2a haploinsufficiency, have revealed its role as a tumor suppressor, mainly through its impact on the mTORC2 pathway. Understanding Ubxn2a provides valuable insights into the mechanisms of colorectal cancer development and potential therapeutic strategies.