TES functions as a Mena-dependent tumor suppressor in gastric cancer carcinogenesis and metastasis
TES functions as a Mena-dependent tumor suppressor in gastric cancer carcinogenesis and metastasis
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TES 在胃癌发生和转移中作为 Mena 依赖性肿瘤抑制因子发挥作用
DOI：
10.1186/s40880-019-0347-y
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发表时间：
2019-02
影响因子：
16.2
通讯作者：
Xia Jian-chuan
中科院分区：
文献类型：
--
作者：
Wang Dan-dan;Chen Yi-bing;Zhao Jing-jing;Zhang Xiao-fei;Zhu Guang-chao;Weng De-sheng;Pan Ke;Lv Lin;Pan Qiu-zhong;Jiang Shan-shan;Wang Lei-lei;Xia Jian-chuan
背景在我们以前的研究中，我们在原发性胃癌（GC）中发现了一个候选抑癌基因，testin LIM结构域蛋白（TES）。TES包含三个LIM结构域，它们是细胞粘附和细胞骨架调节蛋白的特异性相互作用区域。Mena是一种已知的细胞骨架调节剂，其调节肌动蛋白丝的组装，并通过与Lamellipodin（Lpd）相互作用来调节细胞粘附和运动性。因此，我们推测TES通过与Mena相互作用而在胃癌中发挥抑癌作用。方法采用体外细胞增殖实验、集落形成实验、细胞周期分析、Transwell实验、体内致瘤性和转移实验等方法，研究TES对胃癌细胞的抑瘤作用。通过基于免疫沉淀的质谱法研究TES和Mena的相互作用。我们还分析了TES和Mena在172例胃癌标本中的表达，采用免疫组化和探讨TES和Mena在GC.ResultsTES抑制胃癌细胞增殖和集落形成，诱导细胞周期阻滞，并抑制体外致瘤性的临床病理和预后意义。此外，它在体外抑制GC细胞的迁移和侵袭，并在体内抑制转移。TES与Mena相互作用，并抑制Mena与Lpd的相互作用。Transwell分析表明TES以Mena依赖性方式抑制GC细胞的迁移和侵袭。在Mena高表达的胃癌患者中，TES的表达与肿瘤浸润（P = 0.005）、淋巴结转移（P = 0.003）、TNM分期（P = 0.003）和预后（P = 0.010）有关。然而，没有显着的关联，观察胃癌患者低Mena expressions.ConclusionsWe认为，TES功能作为一个Mena依赖性肿瘤抑制因子。TES是一个有价值的预后指标和GC治疗的潜在靶点。
BackgroundIn our previous study, we identified a candidate tumor suppressor gene, testin LIM domain protein (TES), in primary gastric cancer (GC). TES contains three LIM domains, which are specific interacting regions for the cell adhesion and cytoskeleton regulatory proteins. Mena is a known cytoskeleton regulator that regulates the assembly of actin filaments and modulates cell adhesion and motility by interacting with Lamellipodin (Lpd). Therefore, we hypothesized that TES plays a role as tumor suppressor in GC through interacting with Mena. This study aimed to investigate the tumor suppressive functions of TES in GC.MethodsWe explored the tumor suppressive effect of TES in GC by in vitro cell proliferation assay, colony formation assay, cell cycle analysis, Transwell assays, and in vivo tumorigenicity and metastasis assays. The interaction of TES and Mena was investigated through immunoprecipitation‐based mass spectrometry. We also analyzed the expression of TES and Mena in 172 GC specimens using immunohistochemistry and investigated the clinicopathological and prognostic significance of TES and Mena in GC.ResultsTES suppressed GC cell proliferation and colony formation, induced cell cycle arrest, and inhibited tumorigenicity in vitro. Additionally, it inhibited GC cell migration and invasion in vitro and suppressed metastasis in vivo. TES interacted with Mena, and inhibited the interaction of Mena with Lpd. Transwell assays suggested that TES suppressed migration and invasion of GC cells in a Mena‐dependent fashion. In GC patients with high Mena expression, the expression of TES was associated with tumor infiltration (P = 0.005), lymph node metastasis (P = 0.003), TNM stage (P = 0.003), and prognosis (P = 0.010). However, no significant association was observed in GC patients with low Mena expression.ConclusionsWe believe that TES functions as a Mena‐dependent tumor suppressor. TES represents a valuable prognostic marker and potential target for GC treatment.
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影响因子：
3
作者：
A. Boddie;C. McBride;C. Balch
通讯作者：
A. Boddie;C. McBride;C. Balch
影响因子：
8
作者：
通讯作者：
--
影响因子：
168.9
作者：
P. Hohenberger;S. Gretschel
通讯作者：
P. Hohenberger;S. Gretschel
DOI：
10.1073/pnas.0504934102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Drusco, A;Zanesi, N;Croce, CM
通讯作者：
Croce, CM
影响因子：
4.2
作者：
Wang, Ming;Wang, Qian;Huang, Li-Nian
通讯作者：
Huang, Li-Nian