Sp5, a member of the Specificity Protein family, is closely associated with the Wnt/β -catenin signaling pathway. Activation of Sp5 in response to Wnt/β -catenin signaling is seen in many species during processes like axis patterning, neural crest induction, and maintenance and differentiation of stem cells [6]. It is also considered a Wnt target gene, and its expression is commonly regulated in various cell types and biological contexts, highlighting its overall biological importance [3,5]. Genetic models can be valuable for studying Sp5's functions in depth.

In prostate cancer cells, CPT1A, a succinyltransferase, promotes the succinylation of Sp5. This strengthens the binding between Sp5 and the promoter of PDPK1, activating PDPK1 transcription, which in turn activates the AKT/mTOR signal pathway, enhancing cell viability and glycolysis [1]. In mouse embryonic stem cells (mESCs), Sp5 induces the expression of Nanog, which mediates the self-renewal-promoting effect of Sp5 [2]. In HCT116 colon cancer cells, Sp5 negatively regulates cell proliferation by upregulating the transcription of p27, suggesting that these cells downregulate Sp5 to avoid growth arrest [5]. In lung adenocarcinoma, Wnt inhibitor Sp5 facilitates SERPING1 transcription by binding to its gene promoter, and SERPING1 suppresses tumor progression via the TSC2/mTOR pathway [4].

In summary, Sp5 has diverse functions in different biological processes. Through model-based research, it has been shown to play crucial roles in cancer-related processes such as cell viability, glycolysis, and proliferation, as well as in maintaining stem cell self-renewal. The findings from various models contribute to understanding the underlying mechanisms in diseases like prostate cancer, colon cancer, and lung adenocarcinoma, potentially providing novel targets for diagnosis or therapy.