文章：

TBL1XR1参与c-Met介导的人非小细胞肺癌的肿瘤发生

TBL1XR1 is involved in c-Met-mediated tumorigenesis of human nonsmall cell lung cancer 

原文发布日期：2019-06-27 

英文摘要：

Nonsmall cell lung carcinoma (NSCLC) contributes to the highest number of cancer deaths globally. Metastases and chemoresistance are two major confounders to the treatment efficacy in NSCLC. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been associated with high rates of metastases in breast, gastric, and stomach cancers. However, the role of TBL1XR1 in lung cancers remains underexplored. We selected matched and cancerous lung tissues to establish the upregulation of TBL1XR1. Using in vitro assays, we assessed the influence of TBL1XR1 on various cancer phenotypes, namely cell proliferation, chemoresistance, invasion, and metastases in a CRISPR-Cas9-mediated knock out model (A549 cells), and H460 cell lines overexpressing TBL1XR1. We found that TBL1XR1 is overexpressed in NSCLC tissue and patient sera in comparison to paired adjacent normal tissue. Overexpression of TBL1XR1 in NSCLC cell lines mediates cell survival, proliferation, and metastases. TBL1XR1 was found to regulate MEK and Akt pathways through their master regulator c-Met. We observed that activation of c-Met is downregulated in the absence of TBL1XR1. Our study strengthens the contention that TBL1XR1 is a biomarker for prognosis of NSCLC. It may also be considered as an adjunct or core therapeutic target to overcome cisplatin resistance in lung cancers. 

摘要翻译： 

非小细胞肺癌（NSCLC）是全球癌症死亡的首要原因。转移和化疗耐药性是影响NSCLC治疗效果的两个主要因素。转导素（β）样1-X连锁受体1（TBL1XR1）已被证实与乳腺癌、胃癌的高转移率相关，但该基因在肺癌中的作用尚未明确。本研究通过配对癌组织与癌旁组织对照，证实TBL1XR1在肺癌中表达上调。我们采用CRISPR-Cas9介导的基因敲除模型（A549细胞）及过表达TBL1XR1的H460细胞系，通过体外实验评估了TBL1XR1对多种癌症表型的影响，包括细胞增殖、化疗耐药性、侵袭和转移能力。研究发现：与配对癌旁正常组织相比，TBL1XR1在NSCLC组织及患者血清中显著高表达；其在NSCLC细胞系中的过表达会介导细胞存活、增殖和转移过程；TBL1XR1通过上游调控因子c-Met调控MEK和Akt信号通路，且c-Met的激活在TBL1XR1缺失时受到抑制。本研究强化了TBL1XR1作为NSCLC预后生物标志物的论证价值，并提示其可作为辅助或核心治疗靶点以克服肺癌顺铂耐药问题。

原文链接：

TBL1XR1 is involved in c-Met-mediated tumorigenesis of human nonsmall cell lung cancer