Zeb1, also known as zinc finger E-box binding homeobox 1, is a key transcription factor in epithelial-mesenchymal transition (EMT). EMT is a process where epithelial cells acquire mesenchymal characteristics, which is involved in numerous biological processes like embryonic development, fibrosis, and tumor progression [4,5]. Zeb1 is associated with multiple signaling pathways, such as those related to tumor metabolism and immune escape. Genetic models, especially gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Zeb1's functions.

In cancer research, multiple studies have revealed Zeb1's significance. In osteosarcoma, miR-144-3p can promote ferroptosis and inhibit tumor cell proliferation, migration, and invasion by negatively regulating Zeb1 expression [1]. In hepatocellular carcinoma (HCC), Zeb1 transcriptionally activates PFKM, enhancing the Warburg effect and facilitating tumorigenesis and metastasis. Knockdown of Zeb1 in HCC cell lines leads to impaired glycolysis, proliferation, and invasion, which can be rescued by exogenous PFKM expression [2]. In breast cancer, Zeb1 promotes the Warburg effect by increasing the transcriptional expression of glycolytic rate-determining enzymes, and also induces M2 macrophage polarization, contributing to an immunosuppressive tumor microenvironment [3].

In conclusion, Zeb1 plays essential roles in EMT-related biological processes and is closely associated with cancer development. The use of KO/CKO mouse models in these studies has provided insights into how Zeb1 influences tumor-related metabolic reprogramming, immune escape, and cell-cell interactions in the tumor microenvironment. Understanding Zeb1's functions can potentially offer new therapeutic strategies for cancer treatment.