Usp37, an ubiquitin-specific peptidase, is a deubiquitinating enzyme (DUB). DUBs are involved in the stem-cell pathway network and chemo-resistance in cancer. Usp37 participates in regulating protein stability by removing ubiquitin chains from target proteins, and is associated with pathways like Hedgehog (Hh), which is crucial for embryonic development and tissue homeostasis [1].

In breast cancer, knockdown of Usp37 in cell lines and in vivo mouse models inhibited tumorigenicity, regulated cell invasion, epithelial-mesenchymal transition (EMT), stemness, and cisplatin sensitivity, and down-regulated Hh pathway components Smo and Gli-1 [1]. In DNA damage response, Usp37 knockdown in breast cancer cells increased BLM polyubiquitination, accelerated its proteolysis, impaired DNA damage response, enhanced DNA damage, and sensitized cells to DNA-damaging agents in cell culture and in vivo mouse models [2]. In colorectal cancer, Usp37 silencing in nude mice suppressed tumor growth and lung metastasis, and in vitro experiments showed it regulated cell proliferation, cycle, apoptosis, migration, invasion, EMT, and stemness [3].

In conclusion, Usp37 plays a significant role in multiple biological processes and diseases, especially in cancer. Through gene knockout or knockdown in in vivo models like mouse models, its functions in promoting tumor progression, regulating DNA damage response, and affecting angiogenesis and metastasis have been revealed. These findings suggest Usp37 could be a potential therapeutic target for treating certain cancers.