Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity
Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity
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Bif-1通过Cdc42表达和活性促进肿瘤细胞迁移和转移
DOI：
10.1007/s10585-016-9825-7
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发表时间：
2016
影响因子：
4
通讯作者：
Hongyang Wang
中科院分区：
文献类型：
--
作者：
Cunzhen Zhang;Fenghua Liu;Haiyang Chen;Nan Li;Weixing Guo;D;an Huang;Shanhua Tang;Honggang Wang;Shuqun Cheng;Zhong Li;Hongyang Wang
肿瘤转移是肿瘤细胞从肿瘤中播散并进入附近和远处微环境进行新定殖的过程。据报道，Bif-1（BAX 相互作用因子 1）具有 BAR 结构域和 SH3 结构域，参与细胞生长、凋亡和自噬。然而，Bif-1对转移的影响研究较少。为了了解 Bif-1 在转移中的作用，我们使用免疫组织化学、组织微阵列和定量 PCR 研究了人类 HCC 标本中 Bif-1 的表达水平。在迁移和易位测定以及肺转移动物模型中评估了 Bif-1 的功能。使用免疫印迹分析和染色质免疫沉淀确定 Bif-1 和 Rho 家族之间的关系。结果显示，Bif-1在肝细胞癌（HCC）中的表达高于相匹配的癌旁非肿瘤肝组织。 Bif-1表达增加与肿瘤大小以及HCC的细胞间扩散和转移相关。分析 Bif-1 表达与患者临床特征之间的关系发现，Bif-1 水平较高的患者无病生存率和总生存率较短。用 RNAi 敲除 Bif-1 可抑制 HCC 细胞的迁移和肺转移，并降低 Rho 家族成员 Cdc42 的表达。 Bif-1定位于细胞质和细胞核，与Cdc42的启动子转录区相互作用，可能调节Cdc42的表达。我们的结果证明了 Bif-1 在 HCC 中的新作用，其中 Bif-1 通过调节 Cdc42 表达和活性来促进细胞转移。
Tumor metastasis is the process by which tumor cells disseminate from tumors and enter nearby and distant microenvironments for new colonization. Bif-1 (BAX-interacting factor 1), which has a BAR domain and an SH3 domain, has been reported to be involved in cell growth, apoptosis and autophagy. However, the influence of Bif-1 on metastasis has been less studied. To understand the role of Bif-1 in metastasis, we studied the expression levels of Bif-1 in human HCC specimens using immunohistochemistry, a tissue microarray and quantitative PCR. The function of Bif-1 was assessed in migration and translocation assays and the pulmonary metastatic animal model. The relationship between Bif-1 and the Rho family was determined using immunoblot analyses and chromatin.immunoprecipitation. The results showed that the expression of Bif-1 was higher in hepatocellular carcinoma (HCC) than matched adjacent non-tumor liver tissues. Increased Bif-1 expression was associated with tumor size and the intercellular spread and metastasis of HCC. Analysis of the relationship between Bif-1 expression and patients’ clinical characteristics revealed that patients with higher levels of Bif-1 had shorter disease-free and overall survival rates. Knockdown of Bif-1 with RNAi suppressed the migration of HCC cells and pulmonary metastasis and decreased the expression of Cdc42, a member of the Rho family. Bif-1 localized to the cytosol and nucleus and interacted with the promoter transcription region of Cdc42, which may regulate Cdc42 expression. Our results demonstrate a novel role of Bif-1 in HCC, in which Bif-1 promotes cell metastasis by regulating Cdc42 expression and activity.
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影响因子：
6.2
作者：
Coppola, Domenico;Khalil, Farah;Eschrich, Steven A.;Boulware, David;Yeatman, Timothy;Wang, Hong-Gang
通讯作者：
Wang, Hong-Gang
影响因子：
21.3
作者：
Li, Z;Dong, XM;Wu, DQ
通讯作者：
Wu, DQ
影响因子：
13.3
作者：
Ku, Bonsu;Woo, Jae-Sung;Oh, Byung-Ha
通讯作者：
Oh, Byung-Ha
影响因子：
1.7
作者：
Scott M. Schlauder;K. Calder;F. Khalil;Leslie M Passmore;Rahel A Mathew;M. Morgan
通讯作者：
Scott M. Schlauder;K. Calder;F. Khalil;Leslie M Passmore;Rahel A Mathew;M. Morgan
影响因子：
4.8
作者：
Cuddeback, SM;Yamaguchi, H;Wang, HG
通讯作者：
Wang, HG