TFF3, also known as trefoil factor 3 or intestinal trefoil factor, is a protein-coding gene. The TFF3 protein is a small secretory protein expressed on various mucosal surfaces, involved in proper mucosal function and recovery, potentially via immune response-related mechanisms [5]. It has been associated with multiple signaling pathways such as HIF-1α/VEGFA, STAT3-PTGS2, and Hippo-YAP, and is implicated in numerous biological processes and diseases.

In cancer research, TFF3 has been shown to have diverse roles. In pituitary adenoma, overexpression of TFF3 enhanced cell proliferation, migration, invasion, and angiogenesis, likely through the HIF-1α/VEGFA signaling pathway [1]. In colorectal cancer, upregulated TFF3 predicted a worse overall survival rate, and via binding to CD147, it activated STAT3 and PTGS2 expression, promoting cancer cell migration, proliferation, and invasion [2]. In lung adenocarcinoma, TFF3 conferred both intrinsic and acquired resistance to EGFR-TKI therapy, with YAP being positively regulated by TFF3 responsible for the acquired resistance [4]. In ER+ mammary carcinoma, TFF3 was identified as a driver of anti-estrogen-induced dormancy, and combined inhibition of TFF3 and CDK4/6 showed potential in treating this dormant cancer [6]. In addition, TFF3 levels in serum and urine of kidney transplant patients may have diagnostic value, and there are correlations between TFF3 levels and creatinine or eGFR values [3].

In conclusion, TFF3 is a significant gene involved in mucosal function, and its dysregulation is associated with various cancers and kidney transplant-related conditions. Research using gene-knockout (KO) or conditional-knockout (CKO) mouse models, like the Tff3-deficient mouse model used to study its role in hepatic fat accumulation [5], could further clarify its functions in normal and disease states, providing potential therapeutic targets for related diseases.