Foxc2, a member of the forkhead box family of transcription factors, is essential for embryonic and prenatal development [5]. It acts as a crucial modulator during both angiogenesis and lymphangiogenesis via multiple angiogenic and lymphangiogenic pathways [5]. Genetic models, such as KO/CKO mouse models, have been instrumental in studying its functions.

In mouse models, podocyte-specific deletion of Foxc2 led to early proteinuria, podocyte foot process effacement, and microvillus transformation, highlighting its critical role in podocyte function [6]. In cancer research, increased FOXC2 expression in human solid tumors was related to shorter overall survival, lymph node metastases, and TNM stage, making it a promising prognostic marker and potential molecular target [3]. FOXC2 also promotes vasculogenic mimicry in diverse solid tumor types, endowing tumors with resistance to anti-angiogenic therapy, and its suppression can augment the response [1,4]. Additionally, FOXC2 is involved in promoting chemoresistance in cancer through multiple mechanisms, including epithelial-mesenchymal transition, induction of multidrug transporters, activation of the oxidative stress response, and deregulation of cell survival signaling pathways [2].

In conclusion, Foxc2 plays essential roles in embryonic development, podocyte function, and is significantly involved in cancer-related processes such as vasculogenic mimicry, chemoresistance, and metastasis. The use of KO/CKO mouse models has been key in revealing these functions, contributing to our understanding of diseases related to Foxc2 dysregulation and potentially guiding future therapeutic strategies.