TIF1γ Controls Growth And Metastasis Of Hepatocellular Carcinoma Through Inhibition Of TGF-β Signaling

Hepatocellular carcinoma (HCC) is one of the most prevalent cancer types and the third leading cause of death from cancer worldwide. HCC has a very poor prognosis for its characteristics of frequent intrahepatic spread and extrahepatic metastasis. The molecular mechanism of HCC metastasis is still poorly understood. The RBCC/TRIM family protein TIFly plays a critical role during embryonic development, hematopoiesis and maturation of immune cells. In our study, we show that low TIFly protein expression in primary HCC tissues was associated with significantly worse survival and early tumor recurrence in postoperative HCC patients. Multivariate analysis revealed that reduced expression of TIFly was an independent prognostic indicator for overall survival and cumulative recurrence. Knockdown of TIFly in HCC cells promoted cell migration and invasiveness in vitro and HCC metastasis in nude mice while overexpression of TIF1y in HCC cells reduced these processes. TIFly’s anti-metastasis activity was most likely attributed to its inhibition of TGF-β/Smad signaling, which subsequently reduced cell migration and invasiveness in HCC cells. Conclusion:TIFly inhibits HCC cell invasion and metastasis through inhibition of TGF-β/Smad signaling. TIFly may serve as a novel prognostic marker and therapeutic target for HCC.