Foxc2, a member of the forkhead box family of transcription factors, is crucial for embryonic and prenatal development. It acts as a key modulator in angiogenesis and lymphangiogenesis via multiple related pathways [7].

In cancer research, Foxc2 has emerged as an oncogene. High Foxc2 expression in human solid tumors is associated with shorter overall survival, lymph node metastases, TNM stage, and age, making it a promising prognostic and target marker [3]. It promotes vasculogenic mimicry (VM) in diverse solid tumors, driving ectopic expression of endothelial genes in tumor cells under hypoxia, and VM-proficient tumors are resistant to anti-angiogenic therapy [1,6]. Additionally, Foxc2 contributes to chemoresistance in cancer by promoting epithelial-mesenchymal transition, inducing multidrug transporters, activating the oxidative stress response, and deregulating cell survival signaling pathways [2]. In ovarian cancer, it promotes metastasis, lipid metabolism, and cisplatin chemoresistance via the FOXC2/ITGB6 signaling axis [4]. In hepatic stellate cells, the FOXC2-AS1/FOXC2 axis mediates matrix stiffness-induced trans-differentiation into fibrosis-promoting myofibroblasts [5].

In conclusion, Foxc2 plays essential roles in embryonic development, angiogenesis, and lymphangiogenesis. Its dysregulation is closely associated with various cancer-related processes, such as metastasis, chemoresistance, and vasculogenic mimicry. Research on Foxc2 using in vivo models like KO/CKO mouse models has provided valuable insights into its function in these disease-related biological processes, guiding potential prognostic and therapeutic strategies in cancer treatment.