Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.

Background and Objective: UFM1 system, i.e., UFMylation, is a newly identified post-translational modification (PTM). Increasing evidence have indicated that defects of UFMylation are implicated in multiple pathological conditions including cancers. Through this narrative review, we aim to provide a comprehensive view for development of therapeutic targets and strategies. Methods: Based on PubMed database, thorough literature research was performed to finish this narrative review. The research strategy was as follows: (ufmylation) AND ((cancer) OR (neoplasm) OR (tumor)). Key Content and Findings: We first summarize recently identified substrates of UFMylation. Next, we focus on and discuss reported molecular mechanisms of UFMylation in tumorigenesis and cancer treatment responses and resistance. In addition, we discuss the role and function of UFMylation in various cancers, mainly in solid tumors. Lastly, we discuss the possible crosstalk between UFMylation and ubiquitination. Conclusions: In the past decades, emerging evidence have shown that UFMylation is crucial for organ development, homeostasis maintenance, inflammation, immunity and metabolism. In addition, the defects of UFMylation, including genetic variants, abnormal expression pattern and somatic copy number alterations, have been reported involved in tumorigenesis, progression and treatment response. With in-depth investigation and research, enzymatic cascades and substrates of UFMylation will be unveiled. Promisingly, UFMylation may be utilized as a biomarker for diagnosis, treatment response assessment, and therapeutic targets in cancer therapy.