Functionally analyzing the important roles of hepatocyte nuclear factor 3 (FoxA) in tumorigenesis.

Abstract Transcriptional factors (TFs) play a central role in governing gene expression under physiological conditions including the processes of embryonic development, metabolic homeostasis and response to extracellular stimuli. Conceivably, the aberrant dysregulations of TFs would dominantly result in various human disorders including tumorigenesis, diabetes and neurodegenerative diseases. Serving as the most evolutionarily reserved TFs, Fox family TFs have been explored to exert distinct biological functions in neoplastic development, by manipulating diverse gene expression. Recently, among the Fox family members, the pilot roles of FoxAs attract more attention due to their functions as both pioneer factors and transcriptional factors in human tumorigenesis, particularly in the sex-dimorphism tumors. Therefore, the pathological roles of FoxAs in tumorigenesis have been well-explored in modulating inflammation, immune response and metabolic homeostasis. In this review, we comprehensively summarize the impressive progression of FoxAs functional annotation, clinical relevance, upstream regulators and downstream effectors, as well as valuable animal models, and highlight the potential strategies to target FoxAs for cancer therapies.