The expression and role of trefoil factors in human tumors

Yifan Zhang, Yang Liu, Lei Wang, Haiyan Song


Trefoil factor (TFF) family is a type of small secreted peptide characterized by a stable trefoil structure, and it includes three members: TFF1, TFF2 and TFF3. TFFs were initially found mainly distributed in the gastrointestinal mucosa and were subsequently found in the uterus, breast, hypothalamus, pituitary, respiratory tract, conjunctiva and other tissues, with the biological function of mucosal protection, epithelial restitution, inflammatory regulation, etc. Recent studies have found that TFFs’ expression was up-regulated in multiple malignant tumors, including gastric cancer, colon cancer, hepatocellular carcinoma (HCC), breast cancer, prostate cancer, etc. In addition, TFFs’ levels in these tumor tissues or in the serum of patients were closely correlated with malignancy and prognosis. TFFs promote tumorigenesis and metastasis by enhancing cell proliferation, invasion, metastasis, and angiogenesis and by inhibiting cell apoptosis. On the contrary, several recent studies have shown a down-regulation of TFFs in some cancers, and a tumor suppressing role of TFFs through the inhibition of tumor cell proliferation and the promotion of apoptosis. Do TFFs play a tumor-promoting or tumor-inhibiting role? Can they be used as a reliable biomarker for tumor diagnosis and prognosis, or as a treatment target? What is the underlying regulatory mechanism? Currently, these questions still need to be elucidated. This review summarizes current studies about the expression and role of TFFs in human tumors.