TES 作为 Mena 的依赖性抑癌基因在胃癌的发生和转移中起作用。
TES functions as a Mena-dependent tumor suppressor in gastric cancer carcinogenesis and metastasis.
机构信息
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, Guangdong, P.R. China.
Department of Biotherapy, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P.R. China.
出版信息
Cancer Commun (Lond). 2019 Feb 6;39(1):3. doi: 10.1186/s40880-019-0347-y.
BACKGROUND
In 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.
METHODS
We 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.
RESULTS
TES 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.
CONCLUSIONS
We believe that TES functions as a Mena-dependent tumor suppressor. TES represents a valuable prognostic marker and potential target for GC treatment.
背景
在我们之前的研究中，我们在原发性胃癌（GC）中鉴定了一个候选肿瘤抑制基因，即测试 LIM 结构域蛋白（TES）。TES 包含三个 LIM 结构域，这是细胞黏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，通过与 Lamellipodin（Lpd）相互作用来调节肌动蛋白丝的组装，并调节细胞黏附和运动。因此，我们假设 TES 通过与 Mena 相互作用在 GC 中发挥肿瘤抑制作用。本研究旨在探讨 TES 在 GC 中的肿瘤抑制功能。
方法
我们通过体外细胞增殖试验、集落形成试验、细胞周期分析、Transwell 试验以及体内致瘤性和转移试验探索 TES 在 GC 中的肿瘤抑制作用。通过免疫沉淀-质谱分析研究了 TES 和 Mena 的相互作用。我们还使用免疫组织化学分析了 172 例 GC 标本中 TES 和 Mena 的表达，并研究了 TES 和 Mena 在 GC 中的临床病理和预后意义。
结果
TES 抑制 GC 细胞增殖和集落形成，诱导细胞周期停滞，并在体外抑制致瘤性。此外，它还抑制 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 试验表明，TES 以 Mena 依赖的方式抑制 GC 细胞的迁移和侵袭。在 Mena 高表达的 GC 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）相关。然而，在 Mena 低表达的 GC 患者中，没有观察到显著相关性。
结论
我们认为 TES 作为 Mena 依赖性肿瘤抑制因子发挥作用。TES 是一个有价值的预后标志物，也是 GC 治疗的潜在靶点。
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