THE FUNCTIONAL ROLE OF TREFOIL FACTOR 3 IN HUMAN HEPATOCELLULAR CARCINOMA

Abstract

TREFOIL FACTOR 3 (TFF3) HAS BEEN OBSERVED TO BE INVOLVED IN THE PROGRESSION OF HCC, LITTLE IS KNOWN ABOUT WHETHER TFF3 DIRECTLY CONTRIBUTES TO THE MALIGNANT BEHAVIOR OF HCC. IN THIS STUDY, TFF3 WAS OBSERVED TO BE ASSOCIATED WITH POORER PROGNOSIS IN HCC PATIENTS. CELL PROLIFERATION, CELL SURVIVAL, CELL ANCHORAGE-INDEPENDENT GROWTH, AND 3D CELL GROWTH WERE INCREASED OR DECREASED IN HCC CELLS WITH FORCED OR DEPLETED EXPRESSION OF TFF3. TFF3 EXPRESSION IN HCC CELLS ALSO CONCORDANTLY MODULATED IN VIVO TUMOR FORMATION IN NUDE MICE. MOREOVER, HCC CELLS WITH FORCED EXPRESSION OF TFF3 EXHIBITED INCREASED CHEMORESISTANCE AND ENHANCED CANCER STEM CELL-LIKE BEHAVIOR. THE INCREASED ONCOGENICITY OF TFF3 IN HCC CELLS WAS OBSERVED TO BE MEDIATED BY AKT-DEPENDENT INCREASED EXPRESSION OF BCL-2. THESE RESULTS SUGGESTED THAT TFF3 PROMOTES PROGRESSION OF HCC AND MAY SERVE AS A POTENTIAL THERAPEUTIC TARGET IN HCC TREATMENT.