【佳学基因检测】基因检测神经元蛋白阐述促进直肠癌进展的靶标

基因变异引起的肿瘤恶化的原理

学习记录《J Exp Clin Cancer Res》在. 2022 Sep 2;41(1):266.发表了一篇题目为《神经元蛋白 Neuroligin 1 通过调节 APC/β-catenin 通路促进结直肠癌进展》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Margherita Pergolizzi , Laura Bizzozero , Federica Maione, Elena Maldi, Claudio Isella, Marco Macagno, Elisa Mariella, Alberto Bardelli, Enzo Medico, Caterina Marchiò, Guido Serini, Federica Di Nicolantonio, Federico Bussolino, Marco Arese 等完成。促进了肿瘤的精准治疗选择与直肠癌恶化的作用靶点，基因检测结果的应再次丰富全面。

肿瘤靶向药物及精准治疗临床研究内容关键词：

转移相关基因,直肠癌,总生存期,预后

肿瘤靶向治疗基因检测临床应用结果

结直肠癌恶化进展的基因检测研究背景：结直肠癌 (CRC) 在转移阶段诊断时仍然很大程度上无法治愈。尽管近年来针对这种疾病的精准医学取得了一些进展，但仍然非常需要新的分子靶点以及预后/预测标志物。 肿瘤的基因解码研究表明Neuroligin 1 (NLGN1) 是一种跨膜蛋白，在突触处与肿瘤抑制性腺瘤性息肉病 (APC) 相互作用，APC 与 CRC 的发病机制密切相关，是 WNT/β-catenin 通路的关键参与者。结直肠癌恶化进展的基因检测研究方法：在对人类 CRC 样本进行 NLGN1 表达研究后，在结直肠癌恶化进展的基因检测研究中，基因解码基因检测使用体外和体内方法来研究 CRC 细胞外渗和转移形成能力。在分子水平上，研究了 APC 和 NLGN1 在癌症背景下的功能联系。结直肠癌恶化进展的基因检测研究结果：这里基因解码基因检浊显示 NLGN1 在人类结直肠肿瘤中表达，包括侵袭性迁移（出芽）的单个肿瘤细胞簇和血管栓子。基因解码基因检测发现 NLGN1 在体外促进 CRC 细胞穿过内皮单层（即跨内皮迁移或 TEM），以及两种小鼠模型中的细胞外渗/肺侵袭和不同的器官转移。从机制上讲，NLGN1 促进 APC 定位到细胞膜并与该蛋白的一些同种型共免疫沉淀，刺激 β-连环蛋白易位至细胞核，上调间充质标志物和 WNT 靶基因，并在 CRC 细胞系中诱导“EMT 表型”。总之，结直肠癌的恶化机制基因解码发现了一种新的 CRC 侵袭性调节剂，它影响该疾病的关键发病途径，并可能代表一种新的治疗靶点，并具有继承神经生物学领域大量知识的额外好处。神经素 1； WNT通路；内渗/外渗；转移;肿瘤出芽。

肿瘤发生与复发转移国际数据库描述：

Background: Colorectal cancer (CRC) remains largely incurable when diagnosed at the metastatic stage. Despite some advances in precision medicine for this disease in recent years, new molecular targets, as well as prognostic/predictive markers, are highly needed. Neuroligin 1 (NLGN1) is a transmembrane protein that interacts at the synapse with the tumor suppressor adenomatous polyposis Coli (APC), which is heavily involved in the pathogenesis of CRC and is a key player in the WNT/β-catenin pathway.Methods: After performing expression studies of NLGN1 on human CRC samples, in this paper we used in vitro and in vivo approaches to study CRC cells extravasation and metastasis formation capabilities. At the molecular level, the functional link between APC and NLGN1 in the cancer context was studied.Results: Here we show that NLGN1 is expressed in human colorectal tumors, including clusters of aggressive migrating (budding) single tumor cells and vascular emboli. We found that NLGN1 promotes CRC cells crossing of an endothelial monolayer (i.e. Trans-Endothelial Migration or TEM) in vitro, as well as cell extravasation/lung invasion and differential organ metastatization in two mouse models. Mechanistically, NLGN1 promotes APC localization to the cell membrane and co-immunoprecipitates with some isoforms of this protein stimulates β-catenin translocation to the nucleus, upregulates mesenchymal markers and WNT target genes and induces an "EMT phenotype" in CRC cell lines CONCLUSIONS: In conclusion, we have uncovered a novel modulator of CRC aggressiveness which impacts on a critical pathogenetic pathway of this disease, and may represent a novel therapeutic target, with the added benefit of carrying over substantial knowledge from the neurobiology field.Keywords: APC; Neuroligin 1; WNT pathway; intravasation/extravasation; metastasis; tumor budding.

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