Abstract
The 14-3-3 family of proteins are phosphoserine/phosphothreonine-binding proteins. 14-3-3σ (SFN) is a subtype of the 14-3-3 family and is widely present in all tissues and organs of eukaryotes. SFN can regulate various biological activities, such as cell growth, cell division, cell death and cell migration, by binding to different client proteins. These diverse biological functions make SFN a candidate protein that may play a notable role in the development of various diseases. However, its mechanism of action remains unclear, and its role in different diseases is still controversial. DNA methylation is an important epigenetic modification. DNA methylation, under the catalysis of DNA-related modification enzymes, affects gene expression regulation, including the silencing of tumor suppressor genes, oncogene activation, genome stability and the tumor microenvironment. In the present review, how SFN DNA methylation promotes or blocks the carcinogenesis and tumor progression of various cancer types is discussed. The potential clinical value of SFN as a tumor suppressor or cancer-promoting factor in different cancer types for precision cancer medicine is also highlighted.