Role of IQGAP3 in metastasis and epithelial-mesenchymal transition in human hepatocellular carcinoma.
Role of IQGAP3 in metastasis and epithelial-mesenchymal transition in human hepatocellular carcinoma.
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DOI：
10.1186/s12967-017-1275-8
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发表时间：
2017-08-15
影响因子：
7.4
通讯作者：
Jia H
中科院分区：
文献类型：
--
作者：
Shi Y;Qin N;Zhou Q;Chen Y;Huang S;Chen B;Shen G;Jia H
肝细胞癌因其高转移率和复发率而成为世界范围内最致命的癌症之一。癌基因IQ基序含GTP酶激活蛋白3(IQGAP3)在多种人类肿瘤中普遍过表达，包括肝癌、卵巢癌、肺癌、结肠癌、胃癌、骨髓和乳腺癌等，并参与癌细胞的侵袭和转移。因此，我们旨在探讨IQGAP3在肝细胞癌中的生物学作用及其分子机制。我们使用了120例临床肝细胞癌标本、9例肝细胞癌肿瘤组织和4例正常肝组织。采用免疫印迹、定量聚合酶链式反应和免疫组织化学方法检测肝癌细胞系(Hep3B、SMMC-7721、HCCC-9810、HepG2、BEL-7404、HCCLM3、QGY-7701、Huh7和MHCC97H)和正常肝上皮细胞LO2中IQGAP3基因和蛋白的表达。此外，创伤愈合和跨孔基质穿透试验分别用于评估肝癌细胞的迁移和侵袭能力。IQGAP3在肝癌细胞和组织中的表达显著上调。IQGAP3在肝细胞癌中的高表达与侵袭性临床病理特征相关，是影响总生存率的独立不良预后因素。此外，异位表达IQGAP3显著促进肝癌细胞在体外的迁移、侵袭和上皮向间充质转化(EMT)，并促进裸鼠原位肝癌的转移。相反，沉默内源性IQGAP3则表现出相反的效果。机制上，IQGAP3通过激活转化生长因子-β信号通路促进内皮细胞转移和转移。IQGAP3通过结构性激活转化生长因子-β信号通路，在肝细胞癌的转移和转移性转移中发挥重要的调节作用。我们的发现为IQGAP3在EMT和转移中的作用提供了新的证据，表明它作为预测预后的候选生物标记物和抗肝癌的治疗靶点的潜力。
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC. We used 120 archived clinical HCC samples, 9 snap-frozen HCC tumor tissues, and 4 normal liver tissues. Expression of IQGAP3 mRNA and protein in HCC cell lines (Hep3B, SMMC-7721, HCCC-9810, HepG2, BEL-7404, HCCLM3, QGY-7701, Huh7, and MHCC97H) and normal liver epithelial cells LO2 was examined by western blot, quantitative polymerase chain reaction, and immunohistochemistry. In addition, wound-healing and transwell matrix penetration assays were used to assess the migratory and invasive abilities of HCC cells, respectively. Expression of the IQGAP3 was robustly upregulated in HCC cells and tissues. High expression of IQGAP3 in HCC correlated with aggressive clinicopathological features and was an independent poor prognostic factor for overall survival. Furthermore, ectopic expression of IQGAP3 markedly enhanced HCC cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in vitro and promoted metastasis of orthotopic hepatic tumors in nude mice. Conversely, silencing endogenous IQGAP3 showed an opposite effect. Mechanistically, IQGAP3 promoted EMT and metastasis by activating TGF-β signaling. IQGAP3 functions as an important regulator of metastasis and EMT by constitutively activating the TGF-β signaling pathway in HCC. Our findings present new evidence of the role of IQGAP3 in EMT and metastasis, indicating its potential as a prognostic biomarker candidate and a therapeutic target against HCC.
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影响因子：
11.2
作者：
Mohammad KS;Javelaud D;Fournier PG;Niewolna M;McKenna CR;Peng XH;Duong V;Dunn LK;Mauviel A;Guise TA
通讯作者：
Guise TA
影响因子：
3.7
作者：
Qu LS;Liu JX;Liu TT;Shen XZ;Chen TY;Ni ZP;Lu CH
通讯作者：
Lu CH
影响因子：
11.2
作者：
Onder, Tamer T.;Gupta, Piyush B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
影响因子：
13.5
作者：
Fransvea, Emilia;Angelotti, Umberto;Giannelli, Gianluigi
通讯作者：
Giannelli, Gianluigi
影响因子：
6
作者：
Masszi, A;Fan, L;Kapus, A
通讯作者：
Kapus, A