Transducin (β)-like 1 X-linked receptor 1 promotes gastric cancer progression via the ERK1/2 pathway.
Transducin (β)-like 1 X-linked receptor 1 promotes gastric cancer progression via the ERK1/2 pathway.
复制标题
转导蛋白 (β) 样 1 X 连锁受体 1 通过 ERK1/2 途径促进胃癌进展
作者：
Zhou Q;Wang X;Yu Z;Wu X;Chen X;Li J;Zhu Z;Liu B;Su L
胃癌（GC）是全球最常见的癌症之一，肿瘤局部广泛侵袭、转移，预后不良。了解调节GC进展的机制对于制定有效的治疗策略是必要的。转导蛋白 (β) 样 1 X 连锁受体 1 (TBL1XR1) 是控制基因激活和抑制的重要调节因子，被认为与肿瘤发生有关。然而，TBL1XR1 在人类 GC 中的作用仍然很大程度上未知。在这里，我们发现TBL1XR1在人GC组织中异常表达，并且TBL1XR1水平与局部肿瘤侵袭、晚期肿瘤、淋巴结、转移（TNM）分期和不良预后高度相关。 shRNA敲低TBL1XR1可抑制体外GC细胞增殖、迁移、侵袭、上皮间质转化（EMT），以及体内肿瘤发生和腹膜转移，而TBL1XR1过表达则产生相反的作用。这些作用是通过激活 ERK1/2 信号通路介导的，用特定的 ERK1/2 抑制剂 (U0126) 抑制该通路会显着削弱 TBL1XR1 诱导的肿瘤促进作用。此外，TBL1XR1 介导的 ERK1/2 激活依赖于 β-catenin/MMP7/EGFR 信号通路。总之，TBL1XR1通过激活β-catenin/MMP7/EGFR/ERK信号通路促进GC肿瘤的发生和进展，并可能作为GC的新治疗靶点。
Gastric cancer (GC) is one of the most common types of cancer worldwide, and it involves extensive local tumour invasion, metastasis and poor prognosis. Understanding the mechanisms regulating the progression of GC is necessary for the development of effective therapeutic strategies. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is an important regulator controlling gene activation and repression, which has been thought to be involved in tumorigenesis. However, the role of TBL1XR1 in human GC remains largely unknown. Here, we find that TBL1XR1 is aberrantly expressed in human GC tissues, and TBL1XR1 levels are highly correlated with local tumour invasion, late tumor, lymph node, metastasis (TNM) stage and poor prognosis. Knockdown of TBL1XR1 by shRNA inhibits GC cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) in vitro, as well as tumorigenesis and peritoneal metastasis in vivo, whereas overexpression of TBL1XR1 produces the opposite effects. These effects are mediated by activation of the ERK1/2 signalling pathway, and inhibition of this pathway with a specific ERK1/2 inhibitor (U0126) significantly impairs the tumour-promoting effects induced by TBL1XR1. Moreover, TBL1XR1 mediated ERK1/2 activation is dependent on the β-catenin/MMP7/EGFR signalling pathway. In conclusion, TBL1XR1 contributes to GC tumorigenesis and progression through the activation of the β-catenin/MMP7/EGFR/ERK signalling pathway and may act as a new therapeutic target for GC.