TFF1 is a tumor suppressor mainly secreted by the stomach, which regulates the normal differentiation of the gastric glands and protects the gastric mucosa from erosion through interaction with various mucins. The knock-out of Tff1 promotes the activation of the classical NF-kB signaling pathway, which in turn leads to increased inflammation during the formation of gastric cancer. Therefore, Tff1 knock-out mice was a model of spontaneous induced gastric cancer. In addition, TFF1 expression is upregulated and mRNA levels increase in the serum of some specific types of breast cancer patients. However, high expression of TFF1 in triple-negative breast cancer is associated with prolonged survival. TFF1 overexpression can promote apoptosis of tumor cell lines, while TFF1 knockout promotes tumor formation.

Gene targeting strategy for B-hTFF1 mice. The exons 1~3 of mouse TFF1 gene that encodes the full-length protein were replaced by human TFF1 exons 1~3 in B-hTFF1 mice.