TIFA suppresses hepatocellular carcinoma progression via MALT1-dependent and-independent signaling pathways  

作　　者：Wenzhi Shen Renle Du Jun Li Xiaohe Luo Shuangtao Zhao Antao Chang Wei Zhou Ruifang Gao Dehong Luo Juan Wang Na Hao Yanhua Liu Yanan Chen Yunping Luo Peiqing Sun Shengyong Yang Na Luo Rong Xiang 

机构地区：[1]Department of Immunology,School of Medicine,Nankai University,Tianjin,China [2]International Joint Center for Biomedical Research of the Ministry of Education,Tianjin,China [3]Department of Immunology,Institute of Basic Medical Science,Chinese Academy of Medical Science and Peking Union Medical College,Beijing,China [4]Department of Cancer Biology and Comprehensive Cancer Center,Wake Forest University Medical Center,Winston-Salem,North Carolina,USA [5]West China Hospital,Molecular Medicine Research Centre,State Key Lab Biotherapy,Sichuan University,Chengdu,China

出　　处：《Signal Transduction and Targeted Therapy》2016年第1期81-90,共10页信号转导与靶向治疗（英文）

基　　金：This project is supported by the National Basic Research Program(973)of China(No.2013CB967202);the National Natural Science Foundation of China(No.81273331);the National Natural Science Foundation of China(No.81470354);National Natural Science Foundation of China(81301856;NL).

摘　　要：TIFA,also called T2BP,was first identified using yeast two-hybrid screening.Our previous work showed that TIFA suppresses hepatocellular carcinoma(HCC)progression via apoptosis and cell cycle arrest.However,the mechanism by which this TIFA suppression occurs remains unclear.Here we demonstrated that TIFA-induced apoptosis demonstrates two distinct time patterns(i.e.,at 48 h and 47 days)when TIFA reconstitution occurs.Moreover,we found that MALT1(a competitor of TIFA)plays a crucial role in short-duration TIFA reconstitution.In this regard,MALT1 silencing with shRNA markedly enhances TIFA-induced apoptosis in vitro and in vivo.In addition,TIFA overexpression triggers JNK and p38 activation in long-duration TIFA reconstitution through TRAF6 binding.In particular,JNK activation leads to TIFA-induced apoptosis while p38 activation governs TIFA-induced cell cycle arrest by p53-p21 signaling in vitro and in vivo.Our data suggest a novel mechanism by which TIFA suppresses HCC progression via both MALT1-dependent and MALT1-independent signaling pathways.This may provide insights into a novel targets where HCC progression may be vulnerable to clinical treatment.

关 键 词：MALT1 markedly HEPATOCELLULAR 

分 类 号：R73[医药卫生—肿瘤]