Nr2f1, also known as nuclear receptor subfamily 2, group F, member 1 or COUP-TF1, is an orphan nuclear receptor. It plays a significant role in various biological processes and disease conditions. NR2F1 can regulate gene expression and is involved in pathways like WNT-dependent β-catenin signaling. Its abnormal regulation is associated with cancer development and metastasis, highlighting its importance in tumor biology [2].

In early-stage breast cancer, NR2F1 serves as a barrier to early dissemination. Loss of function of NR2F1 in HER2+ early-stage cancer cells, as observed in relevant experiments, increased in vivo dissemination. This was accompanied by decreased E-cadherin expression, activation of WNT-dependent β-catenin signaling, disorganized laminin 5 deposition, and increased expression of epithelial-mesenchymal transition (EMT) genes such as TWIST1, ZEB1, and PRRX1 [2]. Additionally, an NR2F1-specific agonist was found to suppress metastasis by inducing cancer cell dormancy. Treatment with this agonist led to growth arrest of an HNSCC PDX line, human cell lines, and patient-derived organoids in 3D cultures and in vivo, and this effect was lost when NR2F1 was knocked out by CRISPR-Cas9 [1].

In conclusion, Nr2f1 is a crucial factor in cancer-related biological processes, especially in breast cancer metastasis and cancer cell dormancy. The use of gene knockout models, such as the NR2F1 knockout by CRISPR-Cas9, has provided valuable insights into its role in these disease-related mechanisms, helping to better understand the underlying biology and potentially develop new therapeutic strategies.