SPDEF, also known as the prostate-derived ETS factor, is a member of the ETS transcription factor family. It plays important roles in normal organ function and is involved in various biological processes [1,2]. It has been associated with multiple pathways, such as the canonical Wnt signaling pathway as it interacts with β -catenin in colorectal cancer cells [7].

In different cancers, SPDEF shows dual behaviors. In luminal breast cancer, it is upregulated and promotes cancer stem cell-like properties and tumorigenesis by directly promoting GALNT7 transcription [3]. In prostate cancer, its overexpression is associated with aggressive behavior and poor prognosis, and DNA methylation is a mechanism for decreasing its expression during cancer progression [4,6]. In head and neck squamous cell carcinoma, SPDEF acts as a tumor suppressor by transcriptionally activating NR4A1 [5]. In colorectal cancer, SPDEF can induce a quiescent state in cancer cells by disrupting the binding of β -catenin to TCF1 and TCF3 [7].

In conclusion, SPDEF has a complex role in different diseases, especially cancers, with its expression and function varying across cancer types. Studies using different models have helped reveal its functions in tumor development, progression, and metastasis, providing potential targets for cancer diagnosis and therapy.