Foxd1-flox Mouse

Foxd1, a member of the FOX transcription factor family, is crucial for various biological processes. It has been associated with cell reprogramming and is involved in key developmental events such as kidney and retina development, as well as embryo implantation [3,9]. Dysregulation of Foxd1 has been linked to different pathologies, making it a potential diagnostic biomarker and therapeutic target [9].

In cancer research, Foxd1 has shown oncogenic properties. In pancreatic cancer, its overexpression promotes cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis, while knockdown inhibits these functions [1]. In breast cancer, highly expressed Foxd1 in primary tissues is associated with increased circulating tumor cells (CTCs), and overexpressing Foxd1 enhances BC cell migration, CTC formation, and metastasis via an ERK1/2-related signaling cascade [2]. In uveal melanoma, Foxd1 expression is negatively correlated with patient survival, and in vitro studies suggest it may promote tumor growth and invasion [3]. In head and neck squamous cell carcinoma, Foxd1 promotes cell proliferation by blocking cellular senescence and apoptosis through the p21/CDK2/Rb signaling pathway [5]. In prostate cancer, Foxd1 is upregulated, and its knockdown inhibits cell viability, migration, and invasion [6]. A meta-analysis also indicates that high Foxd1 expression is linked to poor overall and disease-free survival, as well as higher TNM stage in various cancers [7]. In clear cell renal cell carcinoma, knockout of Foxd1 in 786-O cells reduces cell growth, alters mitochondrial metabolism and glycolysis, and extends the G2/M phase of the cell cycle, showing its role in regulating cell division [8]. In oral squamous cell carcinoma, the lncRNA FOXD1-AS1 upregulates Foxd1 to promote cancer progression [4].

In conclusion, Foxd1 is essential for normal development and is involved in multiple biological processes. Its dysregulation contributes to the development and progression of various cancers. The use of gene knockout (KO) and conditional knockout (CKO) mouse models, as well as in vitro functional studies, has been crucial in revealing these roles, providing potential targets for cancer treatment and prognosis evaluation.