Tcf4, also known as Transcription Factor-4, is a transcription factor implicated in the WNT signaling pathway. It plays a crucial role in various biological processes as it binds to β -catenin, an effector of the Wnt pathway, and activates the transcription of genes involved in cell proliferation. This interaction makes it a key player in normal development and is also associated with numerous disease conditions [4,5].

In prostate cancer, Tcf4 was found to induce enzalutamide resistance via neuroendocrine differentiation. RNA sequence analysis showed increased Tcf4 expression in enzalutamide-resistant LNCaP cells. Inducible TCF4 overexpression led to enzalutamide-resistance in a mouse xenograft model, and small molecule inhibitors of TCF4 partially reversed this resistance [1].

In colorectal cancer, TCF4 enhances hepatic metastasis by regulating tumor-associated macrophage recruitment and M2 polarization through the CCL2/CCR2 signaling axis. TCF4 deficiency in MC38 cells in a syngeneic mouse model reduced TAM infiltration and M2 polarization at the metastasis site [2].

In osteosarcoma, TCF4 functions as an oncogene. Circ_0004674 promotes osteosarcoma glycolysis and proliferation through the miR-140-3p/TCF4 pathway, as inhibition of miR-140-3p or overexpression of TCF4 could reverse the phenotypic changes in cancer cells induced by circ_0004674 silencing [3].

In conclusion, Tcf4 is a vital transcription factor in the WNT signaling pathway. Its role in disease has been revealed through in vivo studies, especially in mouse models. In prostate, colorectal, and osteosarcoma cancers, Tcf4 is involved in processes like drug resistance, metastasis, and tumor cell metabolism, highlighting its potential as a therapeutic target in these disease areas.