| 1 | TGIF2 promotes the progression of lung adenocarcinoma by bridging EGFR/RAS/ERK signaling to cancer cell stemness显示文摘TGF-β-induced factor homeobox 2(TGIF2)is a transcription regulator that plays essential roles in the regulation of development and cell fate decisions.Aberrant expression of TGIF family proteins has been observed in several cancers,including ovarian,esophageal,and colorectal cancers.Here,we report that TGIF2 mediates the EGFR–RAS–ERK signaling pathway to enhance the stemness of lung adenocarcinoma(LUAD)cells and,therefore,promote the progression and metastasis of LUAD.We found that high TGIF2 expression was closely correlated with tumor growth,lymph node metastasis,and survival of patients with LUAD.Mice bearing TGIF2-silenced H1299 xenografts developed smaller tumors and fewer lung metastases.Importantly,silencing TGIF2 decreased the cancer stem cell(CSC)-like properties in A549 and H1299 cells.Furthermore,we identified that TGIF2 binding to the OCT4 promoter promotes its expression.In both LUAD cells and in vivo LUAD mouse models,we revealed that EGFR–RAS–ERK signaling phosphorylated TGIF2 and increased its stability,which was important for TGIF2-promoted LUAD stemness since phosphorylation-deficient TGIF2 mutants lost these functions.Thus,our study revealed that an important factor,TGIF2,bridges EGFR signaling to the CSC characteristics of LUAD cells,which can be utilized as an effective target for LUAD therapy. | Renle Du Wenzhi Shen Yi Liu Wenjuan Gao Wei Zhou Jun Li Shuangtao Zhao Chong Chen Yanan Chen Yanhua Liu Peiqing Sun Rong Xiang Yi Shi Yunping Luo | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 7 |
| 2 | TIFA suppresses hepatocellular carcinoma progression via MALT1-dependent and-independent signaling pathways显示文摘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. | 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 | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 0 |
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