Foxf2, a member of the forkhead box transcription factors, serves as a transcriptional regulator. It plays crucial roles in embryonic development, metabolism, and is associated with common diseases like stroke and gastroparesis. In embryonic development, it may affect the expression of organ-specific genes to modulate organogenesis. It is also involved in various signal pathways, such as the Wnt/β-catenin pathway [1].

In prostate cancer, increasing prostatic stromal Foxf2 suppresses tumor growth and metastasis by enhancing antitumor immunity, as it attenuates the CAF phenotype and downregulates Cxcl5 [2]. In breast cancer, FOXF2 oppositely regulates stemness in luminal and basal-like breast cancer cells through the Wnt/β-catenin pathway, activating the pathway in luminal cells but repressing it in basal-like cells [3]. In bone-related processes, Foxf2 represses bone formation via the Wnt2b/β-catenin signaling. Osteoprogenitor-specific Foxf2 knockout mice show a high bone mass phenotype due to increased bone formation [4]. In esophageal squamous cell carcinoma, overexpression of FOXF2 inhibits cell proliferation and M2 polarization of tumor-associated macrophages by modulating the RNF144A-FTO axis [5]. In breast cancer bone metastasis, FOXF2 reprograms cancer cells into an osteomimetic phenotype by transactivating the BMP4/SMAD1 signaling pathway and bone-related genes [6]. In cochlear development, FOXF2 is required, as shown by a human variant associated with hearing loss and mouse knockout models having shortened and malformed cochleae [7]. In palate development, Foxf2 controls palatal shelf morphogenesis through regulating multiple transcription factors and extracellular matrix components, as identified by RNA-seq and ChIP-seq in mouse models [8].

In conclusion, Foxf2 is essential for embryonic development, organogenesis, and is involved in multiple disease-related processes. Gene knockout and conditional knockout mouse models have been instrumental in revealing its role in cancer progression, bone formation, cochlear and palate development. These findings provide valuable insights into the pathogenesis of related diseases and potential therapeutic targets.