【佳學基因檢測】基因檢測神經元蛋白闡述促進直腸癌進展的靶標

基因變異引起的腫瘤惡化的原理

學習記錄《J Exp Clin Cancer Res》在. 2022 Sep 2;41(1):266.發(fā)表了一篇題目為《神經元蛋白 Neuroligin 1 通過調節(jié) APC/β-catenin 通路促進結直腸癌進展》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由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。促進了腫瘤的正確治療選擇與直腸癌惡化的作用靶點，基因檢測結果的應再次豐富全面。

腫瘤靶向藥物及正確治療臨床研究內容關鍵詞：

轉移相關基因,直腸癌,總生存期,預后

腫瘤靶向治療基因檢測臨床應用結果

結直腸癌惡化進展的基因檢測研究背景：結直腸癌 (CRC) 在轉移階段診斷時仍然很大程度上無法治好。盡管近年來針對這種疾病的正確醫(yī)學取得了一些進展，但仍然非常需要新的分子靶點以及預后/預測標志物。 腫瘤的基因解碼研究表明Neuroligin 1 (NLGN1) 是一種跨膜蛋白，在突觸處與腫瘤抑制性腺瘤性息肉病 (APC) 相互作用，APC 與 CRC 的發(fā)病機制密切相關，是 WNT/β-catenin 通路的關鍵參與者。結直腸癌惡化進展的基因檢測研究方法：在對人類 CRC 樣本進行 NLGN1 表達研究后，在結直腸癌惡化進展的基因檢測研究中，基因解碼基因檢測使用體外和體內方法來研究 CRC 細胞外滲和轉移形成能力。在分子水平上，研究了 APC 和 NLGN1 在癌癥背景下的功能聯(lián)系。結直腸癌惡化進展的基因檢測研究結果：這里基因解碼基因檢濁顯示 NLGN1 在人類結直腸腫瘤中表達，包括侵襲性遷移（出芽）的單個腫瘤細胞簇和血管栓子?；蚪獯a基因檢測發(fā)現(xiàn) NLGN1 在體外促進 CRC 細胞穿過內皮單層（即跨內皮遷移或 TEM），以及兩種小鼠模型中的細胞外滲/肺侵襲和不同的器官轉移。從機制上講，NLGN1 促進 APC 定位到細胞膜并與該蛋白的一些同種型共免疫沉淀，刺激 β-連環(huán)蛋白易位至細胞核，上調間充質標志物和 WNT 靶基因，并在 CRC 細胞系中誘導“EMT 表型”?？傊?，結直腸癌的惡化機制基因解碼發(fā)現(xiàn)了一種新的 CRC 侵襲性調節(jié)劑，它影響該疾病的關鍵發(fā)病途徑，并可能代表一種新的治療靶點，并具有繼承神經生物學領域大量知識的額外好處。神經素 1； WNT通路；內滲/外滲；轉移;腫瘤出芽。

腫瘤發(fā)生與反復轉移國際數(shù)據(jù)庫描述：

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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